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Galangin, as a Potential Anticancer Agent
Abstract
Cancer is a major global health issue and one of the main causes of mortality worldwide. In recent years, cancer mortality and morbidity rates have risen dramatically due to variety of factors. Despite therapeutic alternatives, chemotherapy medications have major adverse effects and many kinds of drug resistance that severely diminish their effectiveness. Galangin, 3,5,7-trihydroxyflavone, is considered as the bioactive constituent of galangal and honey. In general, galangin exhibits several pharmacological effects, such as anti-inflammatory, antioxidant, anticancer, and antiviral activities. The anticancer effects of galangin are mostly due to its abilities to inhibit cell cycle progression, inhibiting mitogen-activated protein kinase (MAPK), protein kinase B (Akt), or mammalian target of rapamycin (mTOR) activity leading to apoptotic cell death by stimulating caspase-9/8/3 and inhibiting tumor invasion and metastasis by decreasing the upregulation of matrix metalloproteinase-2/-9 (MMP-2/-9). These molecular pathways of galangin are involved in suppressing different malignancies, such as lung cancer, hepatic cancer, breast cancer, ovarian cancer, gastric cancer, colorectal cancer, retinoblastoma, and osteosarcoma. The present work is emphasized on the anticancer mechanisms of galangin.
Graphical abstract
... Cancer is the second worldwide cause of death, next to the cardiovascular illnesses. Current treatments such as surgery, radiotherapy, chemotherapy, hormone replacement therapy, immunotherapeutic interventions, targeted agents, growth signal inhibitors, endogenous angioinhibitors, gene therapy, stem cell therapy, and precision medicine are the main treatment strategies to patients (Akram et al., 2017;Singh et al., 2022). However, due to the short-and longterm side effects, innovation of alternative methods is being developed. ...
... However, due to the short-and longterm side effects, innovation of alternative methods is being developed. For example, natural polyphenols are used as plant-derived bioactive medicines to deal with certain diseases (Singh et al., 2022). One class of these bioactive polyphenolic compounds is the flavonoids, the well-known secondary metabolites and natural anti-oxidants presented in plant kingdoms. ...
A natural anti-oxidant galangin, a flavonoid compound rich in the root of galangal, has been proved to exert anti-proliferation and apoptosis induction towards various cancer cells. However, its activities and molecular mechanism against colorectal cancer cell lines (e.g. HCT-116) is still unclear. The aim of this study was to reveal the inhibition and apoptosis induction of galangin in the HCT-116 cells. The results of CCK-8 assay demonstrated that galangin at 20-160 μmol/L inhibited the HCT-116 cells growth in a dose-time-dependent manner. Galangin changed cell morphology, arrested cell cycle at G 0 /G 1 phase, decreased mitochondrial membrane potential, increased intracellular reactive oxygen species (ROS) and Ca ²⁺ and induced early apoptosis in the HCT-116 cells. Based on western blotting results, on one hand, galangin at 80-160 μmol/L up-regulated pro-apoptotic proteins expression such as AIF, PIG3, and Bax, and induced mitochondrial pathway by up-regulating the levels of cleaved caspase-8, cleaved caspase-7, cleaved caspase-9 and cleaved caspase-3, as well as cleavage of poly (ADP-ribose) polymerase (PARP). On the other hand, galangin also induced endoplasmic reticulum (ER) stress in the cell via up-regulation of CHOP and DR5 and then activation of caspase cascades. The results illustrated that galangin induced apoptosis towards the HCT-116 cells through the ROS- and ER stress-mediated both intrinsic and extrinsic apoptotic pathways.
KEYWORDS: galangin; human colon carcinoma cells; apoptotic mechanism; reactive oxygen species; endoplasmic reticulum stress
... Cancer is the second worldwide cause of death, next to the cardiovascular illnesses. Current treatments such as surgery, radiotherapy, chemotherapy, hormone replacement therapy, immunotherapeutic interventions, targeted agents, growth signal inhibitors, endogenous angioinhibitors, gene therapy, stem cell therapy, and precision medicine are the main treatment strategies to patients (Akram et al., 2017;Singh et al., 2022). However, due to the short-and longterm side effects, innovation of alternative methods is being developed. ...
... However, due to the short-and longterm side effects, innovation of alternative methods is being developed. For example, natural polyphenols are used as plant-derived bioactive medicines to deal with certain diseases (Singh et al., 2022). One class of these bioactive polyphenolic compounds is the flavonoids, the well-known secondary metabolites and natural anti-oxidants presented in plant kingdoms. ...
A natural anti-oxidant galangin, a flavonoid compound rich in the root of galangal, has been proved to exert anti-proliferation and apoptosis induction towards various cancer cells. However, its activities and molecular mechanism against colorectal cancer cell lines (e.g. HCT-116) is still unclear. The aim of this study was to reveal the inhibition and apoptosis induction of galangin in the HCT-116 cells. The results of CCK-8 assay demonstrated that galangin at 20-160 μmol/L inhibited the HCT-116 cells growth in a dose-time-dependent manner. Galangin changed cell morphology, arrested cell cycle at G0/G1 phase, decreased mitochondrial membrane potential, increased intracellular reactive oxygen species (ROS) and Ca2+ and induced early apoptosis in the HCT-116 cells. Based on western blotting results, on one hand, galangin at 80-160 μmol/L up-regulated pro-apoptotic proteins expression such as AIF, PIG3, and Bax, and induced mitochondrial pathway by up-regulating the levels of cleaved caspase-8, cleaved caspase-7, cleaved caspase-9 and cleaved caspase-3, as well as cleavage of poly (ADP-ribose) polymerase (PARP). On the other hand, galangin also induced endoplasmic reticulum (ER) stress in the cell via up-regulation of CHOP and DR5 and then activation of caspase cascades. The results illustrated that galangin induced apoptosis towards the HCT-116 cells through the ROS- and ER stress-mediated both intrinsic and extrinsic apoptotic pathways. KEYWORDS: galangin; human colon carcinoma cells; apoptotic mechanism; reactive oxygen species; endoplasmic reticulum stress
... Galangin (GAL), the bioactive component of galangal and honey, is one of the lesser-known flavonoids but is of considerable medical interest due to its antiviral, antibacterial (Cushnie et al., 2003), and anticancer activities. Recent reviews (Rampogu et al., 2022;Singh et al., 2022) demonstrate that galangal is a promising anticancer agent based on its effects on numerous cancers (e. ...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin-converting enzyme 2 as a host cell's receptor protein. The COVID-19 pandemic had a profound impact on global public health and economies. Although various effective vaccinations and medications are now available to prevent and treat COVID-19, natural compounds derived from medicinal plants, particularly flavonoids, demonstrated therapeutic potential to treat COVID-19 disease. Flavonoids exhibit dual antiviral mechanisms: direct interference with viral invasion and inhibition of replication. Specifically, they target key viral molecules, particularly viral proteases, involved in infection. These compounds showcase significant immu-nomodulatory and anti-inflammatory properties, effectively inhibiting various inflam-matory cytokines. Additionally, emerging evidence supports the potential of flavonoids to mitigate the progression of COVID-19 in individuals with obesity by positively influencing lipid metabolism. This review aims to elucidate the molecular structure of SARS-CoV-2 and the underlying mechanism of action of flavonoids on the virus. This study evaluates the potential anti-SARS-CoV-2 properties exhibited by flavonoid compounds, with a specific interest in their structure and mechanisms of action, as therapeutic applications for the prevention and treatment of COVID-19. Nevertheless, a significant portion of existing knowledge is based on theoretical frameworks and findings derived from in vitro investigations. Further research is required to better assess the effectiveness of flavonoids in combating SARS-CoV-2, with a particular emphasis on in vivo and clinical investigations.
... Galangin (Gal, 3-5-7trihydroxyflavone) is a phytochemical that can be found in the propolis bees and also in the roots of the Albina kalanga plant. The flavonoid 3,5,7-trihydroxyflavone (Galangin; Gal) has been reported to have a variety of biological activities, including antitumor, antimutagenic, antioxidative, bactericidal, and antifibrotic effects 7,8 . Nanotechnology has gained wide popularity in the field of applications because the nanoparticles (NPs) have sizes ranging between 1-100 nm and a large surface area relative to their sizes, which increases their ability to interact with target tissues and cells 9,10 . ...
Galangin (Gal) is a natural flavonoid sourced from the roots of the plant Albina Kalanga. It possesses a variety of pharmacological activities, such as antioxidant, anticancer, and anti-inflammatory. The current study aims to enhance the efficacy of galangin through the use of gold nanoparticles as a drug delivery system against CCl4-induced toxicity in the testicular tissue of male albino mice. Forty-two albino mice were divided into seven groups (6 mice/group), treatment with carbon tetrachloride solution for two weeks by intraperitoneal injection, (1 ml/kg) once a week for all groups except the control group, after which a group was injected with gold nanoparticles and two groups were injected with galangin in two concentrations, and two groups were injected with AuNPs + Gal conjugation solution with two concentrations. The animals' bodies were weighed and blood samples were obtained for testosterone hormone analysis and testicles for the purpose of weighing and histological study at the end of the experiments. The study showed that the testicular tissue of mice treated with CCl4 had a different pathology compared to the control group, the testosterone hormone levels in the CCl4 group were significantly higher than those of the control group. Results from the AuNPs+Gal group showed a significant reduction in the effects of CCl4 toxicity on mice testicles, with testosterone levels are returning to normal and histological testicle structures improving, the ratio of testicle weights to animal body weight in the group injected with AuNPs was significantly higher than that of the control and CCl4 groups. In conclusion, the results revealed that galangin combined with gold nanoparticles could effectively reduced the histological and functional tissue damages caused by CCl4, presenting a promising natural solution that needs to be further developed
... GAL has been linked to several biological actions, including antiinflammatory, antioxidant, anti-proliferative, antimicrobial, antiviral, anti-obesity, and anti-genotoxic effects (Patel et al., 2012). Also, numerous studies have shown its activity against various cancers, including hepatocellular, breast, cervical, lung, gastric, blood cell, head and neck, colorectal, and melanoma cancers (Singh et al., 2022). ...
When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.
... Apigenin is a flavonoid and its formula was observed only in Velame. Many studies have revealed that apigenin has cytostatic and cytotoxic effects on various cancer cells, prevents atherogenesis, hypertension, cardiac hypertrophy, ischemia/reperfusion-induced cardiac injury and autoimmune myocarditis, chemical-induced liver and ischemia/reperfusion injury, asthma, bleomycin-induced pulmonary fibrosis, abnormal behavior and oxygen deprivation, glucose/reperfusion-induced neural cell apoptosis, pancreatitis, type 2 diabetes and its complications, osteoporosis, and collagen-induced arthritis [110]. ...
Honeys can be classified as polyfloral or monofloral and have been extensively studied due to an increased interest in their consumption. There is concern with the correct identification of their flowering, the use of analyses that guarantee their physicochemical quality and the quantification of some compounds such as phenolics, to determine their antioxidant and antimicrobial action. This study aims at botanical identification, physicochemical analyses, and the determination of total polyphenols, chromatographic profile and antiradical and antimicrobial activity of honey from different regions of Minas Gerais. Seven different samples were analyzed for the presence of pollen, and color determination. The physicochemical analyses performed were total acidity, moisture, HMF, reducing sugar, and apparent sucrose. The compound profile was determined by UHPLC/MS, the determination of total phenolics and antiradical activity (DPPH method) were performed by spectrophotometry, and minimum inhibitory and bacterial concentrations were determined for cariogenic bacteria. All honey samples met the quality standards required by international legislation, twenty compounds were detected as the main ones, the polyfloral honey was the only honey that inhibited all of the bacteria tested. Sample M6 (Coffee) was the one with the highest amount of total polyphenols, while the lowest was M4 (Cipó-uva). Regarding the antioxidant activity, M5 (Velame) had the best result and M4 (Cipó-uva) was the one that least inhibited oxidation. Of the polyfloral honeys, there was not as high a concentration of phenolic compounds as in the others. Coffee, Aroeira, Velame and Polyfloral have the best anti-radical actions. Betônica, Aroeira, Cipó-uva and Pequi inhibited only some bacteria. The best bacterial inhibition results are from Polyfloral.
... Literature data describe galangin as a strong anticancer and antimicrobial agent. The molecular pathways of this flavonoid are involved in suppressing various malignancies, including osteosarcoma and cancer of the lung, stomach and liver [23,37,38]. In turn, antimicrobial activity of galangin involved various strains of bacteria and fungi, such as S. aureus, E. coli, K. pneumonia, Bacillus subtilis and Candida albicans [39][40][41]. ...
Edible nuts are an important component of a healthy diet, and their frequent consumption has beneficial impact on human health, including reducing the risk of cardiovascular and neurodegenerative diseases. Moreover, various factors, including cultivar, climate, soil characteristic, storage and treatment have influence on the chemical composition of nuts. Therefore, nine tree nut types and peanuts commonly available on Polish market were evaluated for phenolic profile and mineral elements content. The concentration of individual phenolic compounds, including flavonoids, aromatic acids and caffeic acid phenethyl ester (CAPE) was determined by ultra-high pressure liquid chromatography, while the content of macro-elements and trace minerals was analyzed by atomic absorption spectrometry. The phenolic profile of analyzed nuts substantially varied depending on the type of nut. The highest total content of all analyzed flavonoids was determined in walnuts (114.861 µg/g), while the lowest in almonds (1.717 µg/g). In turn, the highest total content of all tested aromatic acid was determined in pecans (33.743 µg/g), and the lowest in almonds (0.096 µg/g). Epicatechin and cinnamic acid were detected in the highest concentration in tested nuts. Moreover, in examined nuts (except walnuts and Brazil nuts), the presence of CAPE was confirmed. The tested nuts were also characterized by wide variation in element concentrations. Almonds contained high concentration of macro-elements (13,111.60 µg/g), while high content of trace elements was determined in pine nuts (192.79 µg/g). The obtained results indicate that the tested nuts are characterized by a significant diversity in the content of both phenolic compounds and minerals. However, all types of nuts, apart from the well-known source of fatty acids, are a rich source of various components with beneficial effect on human health.
Nanoparticles and nanocomposites with low concentration in the body are non-toxic and can be suitable alternative to antibiotics. Gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), and silver-gold nanocomposite (Ag-Au NCs) were synthesized for the first time using galangin (GA) from Suaeda maritima (SM). A simple method was studied and optimized for the biosynthesis of AuNPs, AgNPs, and Ag-Au NCs using GA of SM. A variety of phytochemical compounds found in SM, such as phenols, convert metal into ions and serve as capping agents. The SM phytochemical analysis indicates a high concentration of GA in leaf shell extract, which is a flavonoid with anti-tumor properties. Characterization of GASMAuNPs, GASMAgNPs, and GASMAg-Au NCs was performed using a variety of spectroscopy and microscopy techniques. Based on transmission electron microscopy and field emission scanning electron microscopy, the size of the GASM-Ag-AuNCs (45 nm), GASM-AgNPs (50 nm) and GASM-AuNPs (7 nm) and was spherical. The cytotoxicity effects of these nanoparticles and nanocomposites on Michigan Cancer Foundation-7 (MCF-7) breast cancer cell lines were studied. GA-SM-Ag-AuNCs reduced the cell viability of MCF-7 breast cancer cell lines. Antibacterial activities were evaluated against Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, and Escherichia coli. GA-SM-Ag-Au NCs had maximum inhibition zones for Escherichia coli and Staphylococcus aureus. The maximum inhibition zones observed with GA-SM-Ag-AuNCs were higher than clindamycin, gentamycin, and tetracycline. The minimum inhibitory concentration (MIC) of GA-SM-Ag-AuNCs against Escherichia coli and Staphylococcus aureus was 15.6 μgmL−1. GA-SM-Ag-AuNCs have powerful antimicrobial potential, while having less cytotoxicity at low concentrations. The GA-SM-Ag-AuNCs reduced the cytotoxicity effects on MCF-7. This study showed that GASM-Ag-AuNCs synthesized using GA of SM has antibacterial and anticancer properties with fewer side effects and significant efficacy, which can be effective as a potential therapy in the future.
Interleukin 12 (IL-12) is a pro-inflammatory cytokine type 1 that has acted as a potential immunotherapy for cancer. The mechanism of IL-12 increases the activity of cytotoxic T cells and Natural Killer (NK) cells, reverse tumor-induced immunosuppression, prevent angiogenesis, and increases lymphocyte and antigen transport. Galangal is one of the natural ingredients that have biological activity as an anticancer and immunomodulator. In this research, researchers wanted to know the potential of the active compound of galangal to activate IL-12 by inhibiting the IL-12 analog, namely SHP-2. This research uses bioinformatics studies using several databases such as RCSB PDB, ChEMBL, Dr. Duke's Phytochemical and Ethnobotanical, UALCAN, OncoLnc and computational analysis using KNIME and MOE software. The SHP-2 structure used is taken from the RCSB PDB with the code 5EHR. The 10 compounds with the highest predictions of inhibiting SHP2 using KNIME were obtained, then molecular docking was performed using MOE and three compounds that had the potential to inhibit SHP-2 were Kaempferide, Galangin, and RiboflavinKeywords: cancer, computing, galangal, Interleukin 12, SHP-2, pharmacology.
Cancer is a global intractable disease, and its morbidity and mortality are increasing year by year in developing countries. Surgery and chemotherapy are often used to treat cancer, but they result in unsatisfactory outcomes, such as severe side effects and drug resistance. With the accelerated modernization of traditional Chinese medicine (TCM), an increasing body of evidence has shown that several TCM components have significant anticancer activities. Astragaloside IV (AS-IV) is considered the main active ingredient of the dried root of Astragalus membranaceus. AS-IV exhibits various pharmacological effects, such as anti-inflammatory, hypoglycemic, antifibrotic, and anticancer activities. AS-IV possesses a wide range of activities, such as the modulation of reactive oxygen species-scavenging enzyme activities, participation in cell cycle arrest, induction of apoptosis and autophagy, and suppression of cancer cell proliferation, invasiveness, and metastasis. These effects are involved in the inhibition of different malignant tumors, such as lung, liver, breast, and gastric cancers. This article reviews the bioavailability, anticancer activity, and mechanism of AS-IV and provides suggestions for further research of this TCM.
Background
Propolis is a resinous product accumulated from several plant sources that possess a wide range of therapeutic properties, including anti-cancer activities. However, the role of honeybee-produced propolis on head and neck squamous carcinoma (HNSCC) is not well understood. The aim of this study was to investigate the effects of Apis mellifera propolis on apoptosis and invasiveness in HNSCC cell lines.
Methods
Ethyl acetate extract of propolis (EAEP) was prepared from A. mellifera beehives using liquid–liquid extraction. High-performance liquid chromatography coupled with electrospray ionization-time of flight-mass spectrometry (HPLC-ESI-TOF-MS) was used to determine the flavonoids in EAEP. Isogenic HNSCC cell lines derived from primary (HN30 and HN4) and metastatic site (HN31 and HN12) were used in this study. The cytotoxicity, apoptosis, invasion, and MMP activity of EAEP on HNSCC cells were determined using an MTT assay, flow cytometry, Matrigel invasion assay, and gelatinase zymography, respectively.
Results
We found that EAEP exhibited cytotoxic activity and induced apoptosis in the HNSCC cell lines. Furthermore, EAEP significantly decreased HNSCC cell invasion by reducing MMP-2 and MMP-9 activity. Two flavonoids, galangin and apigenin, were identified in EAEP by HPLC-ESI-TOF-MS. The results suggest that EAEP promotes apoptosis and exerts anti-invasion potential by inhibiting MMP-2 and MMP-9 activity in HNSCC cell lines. These inhibitory effects may be mediated by galangin and apigenin.
Fully understanding the mechanism of how Cholangiocarcinoma (CCA) development and discovering promising therapeutic drugs are important to improve patients' survival time. This study identifies that microRNA-455-5p (miR-455-5p) targets protein phosphatase 1 regulatory subunit 12A (PPP1R12A), an effect that represses mitogen-activated protein kinase (MAPK) and PI3K/AKT pathway activation, thereby controlling CCA cells survival and metastasis. Moreover, miR-455-5p expression is reduced in CCA tissues and negative correlation with PPP1R12A and PPP1R12A knockdown phenotypic mimics miR-455-5p' effects on CCA cells. Furthermore, we demonstrate that galangin inhibits CCA growth both in vitro and in vivo, which is associated with increased miR-455-5p and repressed PPP1R12A expression. In support, overexpression of miR-455-5p abrogates those galangin-mediated anti-CCA effects. These findings establish an essential role of miR-455-5p in CCA development and galangin may provide a potential therapeutic adjuvant agent for anti-CCA treatment.
Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the in vitro experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity.
Galangin has multiple pharmacological efficacies, such as anti-cancer, anti-inflammation and anti-oxidation. Galangin can be rapidly converted into glucuronidated metabolites in vivo. This study aimed to establish an UFLC-MS/MS analytical method to simultaneously determine the concentrations of two glucuronidated metabolites of galangin, galangin-3-O-β-D-glucuronic acid (GG-1) and galangin-7-O-β-D-glucuronic acid (GG-2) in rat plasma. After oral administration of galangal extract (0.3 g/kg), blood samples were collected from the orbital sinus, then treated by methanol precipitation and further gradient-eluted with Phenomenex Kinetex 2.6 µm XB-C18 column. The mass spectrometer was manipulated in the negative electrospray ionization (ESI) and selected multiple reaction monitoring (MRM) mode for the analytes. The precursor-to-product ion pairs applied for GG-1, GG-2 and chrysin (as the internal standard, IS) were m/z 445.2→269.0, 445.2→268.9 and 253.0→142.9, respectively. The results showed that the linear ranges for both GG-1 and GG-2 were 2.0–2000.0 ng/mL ( r ² > 0.995). The inter- and intra-day precision were 89.3%–109.2%, RSD was less than 15%, and the repeatability was good. The recoveries of both metabolites and IS were over 89%, and matrix effect was within 15%. The validated analytical method was further applied to study the pharmacokinetic profiles of GG-1 and GG-2 in vivo. The pharmacokinetic parameters suggested that T max of GG-1 was equivalent to that of GG-2, and MRT 0-t , t 1/2 of GG-2 were a little higher than those of GG-1. Importantly, AUC 0-t and C max of GG-2 were almost twice as those of GG-1. In short, the validated UFLCMS/MS analytical method was feasible to simultaneously determine two galangin metabolites GG-1 and GG-2 in rat plasma and further analyze in vivo metabolism of galangin.
This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2‐fold to 3‐fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2‐fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
Background
Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis and development of cancer. Skp2, a pivotal component of SCFSkp2 E3 ubiquitin ligase, has been shown to function as an oncogene in GBM invasion that contributes to the EMT process. Thus, we explored whether GLN inhibited Skp2-mediated EMT and the mechanism underlying the Skp2 degradation pathway.
Methods
CCK-8 assay, wound healing assay and transwell assay were used to examine cell proliferation, migration, and invasion after treatment with or without GLN. RT-PCR and Western blotting analysis were performed to evaluate mRNA and protein expression, respectively. Co-immunoprecipitation was conducted to detect ubiquitinated Skp2 levels in vitro and in vivo after GLN treatment. Bioluminescence imaging was performed to examine the intracranial tumor size of U87 xenograft mice. Microscale thermophoresis (MST) experiment was used to detect interactions between Skp2 and GLN.
Results
GLN suppressed GBM cell growth, migration, and invasion, and also downregulated the expression of Skp2 and mesenchymal markers (Zeb1, N-cadherin, snail, vimentin) in vitro. Moreover, the overexpression of Skp2 in GBM cells decreased the effect of GLN on EMT. Furthermore, we demonstrated that GLN degraded skp2 protein through the ubiquitination proteasome pathway and directly interacted with skp2 protein, as shown through the MST assay.
Conclusion
This study is the first to identify Skp2 as a novel target of GLN for the treatment of GBM and report of Skp2 protein degradation in a ubiquitination proteasome pathway. Results from our study indicated the potential of GLN for the treatment of GBM through ubiquitin-mediated degradation of Skp2.
Galangin, a natural flavonoid product derived from the root of galangal, is emerging as a promising anticancer agent against multiple cancers. Yet, whether it also has antitumor effects on cholangiocarcinoma (CCA) and the underlying mechanism is still unknown. Herein, we demonstrate that galangin exhibits multiple antitumor effects on CCA cells including decreases cell viability; inhibits proliferation, migration, and invasion; and induces apoptosis. Moreover, those phenotypic changes are associated with downregulated microRNA-21 (miR-21) expression. To support, overexpression of miR-21 blocks galangin-mediated antisurvival and metastasis effects on CCA cells. Mechanically, galangin increases the expression of phosphatase and tensin homolog (PTEN), a direct target of miR-21, resulting in decreased phosphorylation of AKT, a protein kinase which plays a critical role in controlling survival and apoptosis. In contrast, overexpression of miR-21 abrogates galangin-regulated PTEN expression and AKT phosphorylation. Taken together, these findings indicate that galangin inhibits CCA cell proliferation and metastasis and induces cell apoptosis through a miR-21-dependent manner, and galangin may provide a novel potential therapeutic adjuvant to treat CCA.
Background
Galangin has been extensively studied as the antitumor agent in various cancers. However, the effect of galangin in hepatocellular carcinoma (HCC) remains elusive.
Methods
Using RNA sequencing, the differential expression of lncRNA in human HCC cell line with highly metastatic potential (MHCC97H) cells treated with galangin was investigated. Furthermore, H19 expression pattern was also determined in MHCC97H cells following treatment with galangin. In addition, knockdown and overexpression of H19 was performed to analyze the effect of the expression pattern of H19 on cell apoptosis, cell cycle, migration, and invasion in HCC cells. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. In order to analyze loss expression of H19 in vivo, clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) was used.
Results
Total of 50 lncRNAs were significantly differentially expressed in MHCC97H cells treated with galangin. Besides, the expression of H19 was markedly reduced following treatment with galangin in MHCC97H cells. Compared to the Control group, the galangin‐treated group inhibited cell migration and invasion. Knockdown of H19 expression showed increased cell apoptosis and decreased invasion. In addition, RNA‐seq data also identified 161 mRNA which was significantly differentially expressed following treatment with galangin. To further determine the underlying mechanism, p53 protein was analyzed. Notably, the results indicated that knockdown of H19 and miR675 induced the expression of p53, eventually promoting cell apoptosis in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through reduced the expression of H19 and miR675 in MHCC97H cells. The in vivo result showed that compared to the Con, tumor growth was remarkably suppressed with loss expression of H19 .
Conclusion
Our data suggested that galangin has a crucial role in hepatocarcinogenesis through regulating the expression pattern of H19 .
Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients
undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to
drugs. In recent years, natural compounds have aroused growing attention in cancer treatment.
Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the
growth of a normal ovarian cell line, IOSE 364. The IC50 values of galangin on proliferation of
A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow
cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer
cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via
the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating
the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by
galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is
a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin
up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell
lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased
through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the
apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for
the treatment of platinum-resistant ovarian cancers in humans.
Galangin is a flavonoid from the root of Alpinia officinarum. It has novel anticancer properties. In the current study, ovarian cancer cells SKOV3 were treated with galangin alone, galangin combined with Gold nanoparticles (AuNPs) and AuNPs alone, and cytotoxic activity of these agentswas investigated using MTT viability assay. The expression of apoptosis-related genes p53, caspase-8 was studied using Real time PCR assay. Galangin was tested at different concentrations. AuNPs concentrations were 6.25,12.5, 25, 50 and 100 µg/ml. The study of gene expression showed significant effects on p53, caspase8 in ovarian carcinoma cells. The results of the current study refer to galangin-AuNPs combination is synergistic against to ovarian carcinoma to induce cytotoxicity and cell death via apoptosis, this mechanism enhancing expression of p53, caspase-8. The effects of galangin, AuNPs,combination therapy have potential clinicaluse in the future and could be alternative way to the conventional chemotherapy drug.
Galangin (GG), a flavonoid, elicits a potent antitumor activity in diverse cancers. Here, we evaluated the efficacy of GG in the treatment of human glioblastoma multiforme (GBM) and investigated the molecular basis for its inhibitory effects in the disease. GG inhibited viability and proliferation of GBM cells (U251, U87MG, and A172) in a dose-dependent manner (IC50 = 221.8, 262.5, 273.9 μM, respectively; P < 0.001; EdU, ~40% decrease at 150 μM, P < 0.001), and the number of colonies formed was significantly reduced (at 50 μM, P < 0.001). However, normal human astrocytes were more resistant to its cytotoxic effects (IC50 >450 μM). Annexin-V/PI staining was increased indicating that GG induced apoptosis in GBM cells (26.67 and 30.42%, U87MG and U251, respectively) and associated proteins including BAX and cleaved PARP-1 were increased (~3×). Cells also underwent pyroptosis as determined under phase-contrast microscopy. Knockdown of gasdermin E (GSDME), a protein involved in pyroptosis, alleviated pyroptosis induced by GG through aggravating nuclear DNA damage in GBM cells. Meanwhile, fluorescent GFP-RFP-MAP1LC3B puncta associated with autophagy increased under GG treatment, and transmission electron microscopy confirmed the formation of autophagic vesicles. Inhibition of autophagy enhanced GG-induced apoptosis and pyroptosis in GBM cells. Finally, in an orthotopic xenograft model in nude mice derived from U87MG cells, treatment with GG in combination with an inhibitor of autophagy, chloroquine, suppressed tumor growth, and enhanced survival compared to GG monotherapy (P < 0.05). Our results demonstrated that GG simultaneously induces apoptosis, pytoptosis, and protective autophagy in GBM cells, indicating that combination treatment of GG with autophagy inhibitors may be an effective therapeutic strategy for GBM.
Galangin (3,5,7‑trihydroxyflavone), a natural flavonoid present in plants, has been reported to possess anticancer properties in various types of cancers comprising glioma. The underlying mechanism, however, has not been fully elucidated. CD44, a hall marker in glioma, has been reported to be associated with epithelial-mesenchymal transition (EMT) and angiogenesis, which play important roles in glioma progression. In this study, we aimed to investigate whether galangin can inhibit EMT, angiogenesis and CD44 expression in glioma. We observed that galangin inhibited the proliferation, migration, invasion and angiogenesis of glioma cells in a dose-dependent manner, suppressed the expression of CD44 and inhibited angiogenesis of glioma cells through downregulating vascular endothelial growth factor (VEGF) in HUVECs. In addition, the overexpression of CD44 in U87 and U251 cells partly abolished the effects of galangin on glioma cells. Moreover, galangin suppressed tumor growth in an intracranial glioma mouse model. These results indicate that galangin is a potential novel drug for glioblastoma treatment due to its ability to suppress of CD44, EMT and angiogenesis.
Aim: Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Considering the fact that knowledge on the incidence, mortality of ovarian cancer, as well as its risk factors is necessary for planning and preventing complications, this study was conducted with the aim of examining the epidemiology and risk factors of ovarian cancer in the world.
Materials and methods: In order to access the articles, Medline, Web of Science Core Collection, and Scopus databases were searched from their start to the year 2018. Full-text, English observational studies that referred to various aspects of ovarian cancer were included in the study.
Results: In total, 125 articles that had been published during the years 1925–2018 were entered into the study. Ovarian cancer is the seventh most common cancer among women. Increased risk factors of cancer have led to an upward trend in the incidence of cancer around the world. In 2018, 4.4% of entire cancer-related mortality among women was attributed to ovarian cancer. Although the incidence of cancer is higher among high Human Development Index (HDI) countries, the trend of mortality rate tends to be reversing. Various factors affect the occurrence of ovarian cancer, from which genetic factor are among the most important ones. Pregnancy, lactation, and oral contraceptive pills play a role in reducing the risk of this disease.
Conclusion: This study provides significant evidence about ovarian cancer. Considering the heavy burden of ovarian cancer on women's health, preventive measures as well as health education and early detection in high risk groups of women are highly recommended. Although some risk factors cannot be changed, a focus on preventable risk factors may reduce the risk of ovarian cancer. More studies are needed to explore the role of unclear risk factors in ovarian cancer occurrence.
Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the content of the main polyphenols in a brown propolis extract obtained using a patented extraction method (Multi Dinamic Extraction—M.E.D.) by RP-HPLC-UV-PDA-MSn analysis, followed by the bioavailability of galangin and chrysin, the most abundant polyphenols in the mixture (7.8% and 7.5% respectively), following acute (single bolus of 500 mg/kg containing about 3.65 mg of the polyphenol mixture) and prolonged (100, 250 and 500 mg/kg body for 30 days) oral administration in 30 male 8 weeks old C57BL/6 wild-type mice. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min following the oral bolus. In the prolonged setting, blood samples were obtained after 10, 20 or 30 days of administration. At the end of treatment, expression of antioxidant enzymes (superoxyde dismutase, SOD-1; catalase, CAT; glutathione peroxidase, GSS) was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangine was detectable 5 min after acute administration. At the end of the prolonged treatment SOD-1 was found to have increased significantly, unlike CAT and GSS. Overall, these data suggest that oral administration of whole brown propolis extract is followed by rapid absorption and metabolization of galangin followed by adaptations of the antioxidant first line defense system.
Hepatocellular carcinoma (HCC) is one of the most common cancers and has a high mortality rate in less developed countries, especially in China. Galangin (GA), one of the most important and naturally active flavonoids, extracted primarily from the root of Alpinia officinarum Hance, has been demonstrated to be effective in the treatment of HCC. It is a substance with defensive actions and a broad range of biological properties, including inhibitory effects on bacteria, fungi, viruses, the control of hypertension and diabetes, and chemoprevention of several cancers. Experiments have shown that GA prevents HCC through multiple anti-cancer mechanisms, anti-genotoxic activity against environmental and dietary carcinogens; anti-proliferative effects through reversal of the Warburg effect in HCC; arrest of the cell cycle in the G0/G1 phase; induction of apoptosis via stimulation of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and the mitochondrial-dependent apoptosis pathway; induction of autophagy; and inhibition of angiogenesis, metastasis, and multidrug resistance (MDR). In addition, synergistic effects with other chemotherapy drugs have been demonstrated. Therefore, this review is focused on the anti−HCC mechanisms of GA.
Gastric cancer remains one of the most common and deadly cancers worldwide, especially among older males. Based on GLOBOCAN 2018 data, stomach cancer is the 5th most common neoplasm and the 3rd most deadly cancer, with an estimated 783,000 deaths in 2018. Gastric cancer incidence and mortality are highly variable by region and highly dependent on diet and Helicobacter pylori infection. While strides in preventing and treating H. pylori infection have decreased the overall incidence of gastric cancer, they have also contributed to an increase in the incidence of cardia gastric cancer, a rare subtype of the neoplasm that has grown 7-fold in the past decades. A better understanding of the etiology and risk factors of the disease can help reach a consensus in approaching H. pylori infection. Dietary modification, smoking cessation, and exercise hold promise in preventing gastric cancer, while genetic testing is enabling earlier diagnosis and thus greater survival.
Purpose
To describe the mortality experience of women who die of breast cancer in the 20-year period post-diagnosis using various metrics, including annual mortality rates, Kaplan–Meier survival curves and time-to-death histograms.
Methods
We generated three visual representations of SEER-based and hospital-based breast cancer patient cohorts using three different metrics of mortality.
Results
The greatest impact of most prognostic factors was on the probability of latent metastases present after treatment, but for some factors the primary impact was on the time to death for those women with metastases.
Conclusions
The use of time-to-death statistics to display mortality benefits for treated versus untreated women helps facilitate the distinction between treatments which increase the likelihood of cure and treatments that delay cancer growth.
Aims:
The study aimed to investigate the molecular mechanism of inhibition of proliferation and apoptosis induction by galangin against MCF-7 human breast cancer cells.
Methods:
Cell Counting Kit-8 assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis. The expression level of apoptosis-related proteins (cleaved-caspase-9, cleaved-caspase-8, cleaved-caspase-3, Bad, cleaved-Bid, Bcl-2, Bax, p-phosphatidylinositol 3-kinase [PI3K], and p-Akt) and cell cycle-related proteins (cyclin D3, cyclin B1, cyclin-dependent kinases CDK1, CDK2, CDK4, p21, p27, p53) were evaluated by Western blotting.
Results:
Galangin increased the expression of Bax and decreased the expression of Bcl-2 in a concentration-dependent manner, inhibited cell viability, and induced apoptosis. Meanwhile, the expression of cleavage of caspase-9, caspase-8, caspase-3, Bid, and Bad increased significantly while the expression of p-PI3K and p-Akt proteins decreased. In addition, the protein levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated while the expression levels of p21, p27, and p53 were upregulated significantly.
Conclusion:
Galangin could suppress the viability of MCF-7 cells and induce cell apoptosis via the mitochondrial pathway and PI3K/Akt inhibition as well as cell cycle arrest.
The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation. Functional studies revealed that miR-27a overexpression decreased SMAD2 and SMAD4 mRNA and protein levels. Furthermore, miR-27a contributed to cell proliferation and invasion by inhibiting TGF-β-induced cell cycle arrest. These results suggest that miR-27a may function as an oncogene by regulating SMAD2 and SMAD4 in lung cancer. Thus, miR-27a may be a potential target for cancer therapy. This article is protected by copyright. All rights reserved.
Despite the development of more advanced medical therapies, cancer management remains a problem. Head and neck squamous cell carcinoma (HNSCC) is a particularly challenging malignancy and requires more effective treatment strategies and a reduction in the debilitating morbidities associated with the therapies. Phytochemicals have long been used in ancient systems of medicine, and non-toxic phytochemicals are being considered as new options for the effective management of cancer. Here, we discuss the growth inhibitory and anti-cell migratory actions of proanthocyanidins from grape seeds (GSPs), polyphenols in green tea and honokiol, derived from the Magnolia species. Studies of these phytochemicals using human HNSCC cell lines from different sub-sites have demonstrated significant protective effects against HNSCC in both in vitro and in vivo models. Treatment of human HNSCC cell lines with GSPs, (−)-epigallocatechin-3-gallate (EGCG), a polyphenolic component of green tea or honokiol reduced cell viability and induced apoptosis. These effects have been associated with inhibitory effects of the phytochemicals on the epidermal growth factor receptor (EGFR), and cell cycle regulatory proteins, as well as other major tumor-associated pathways. Similarly, the cell migration capacity of HNSCC cell lines was inhibited. Thus, GSPs, honokiol and EGCG appear to be promising bioactive phytochemicals for the management of head and neck cancer.
Osteosarcoma is the most common malignant bone tumor that frequently affects adolescents. Osteosarcoma cells tend to proliferate and invade other tissues such as those of the lungs. Currently, neoadjuvant chemotherapy is the primary strategy to prevent tumor progression. However, its adverse effects result in poor long-term outcomes. Previous research has shown that galangin exhibits antitumor properties on several types of cancer cells; however its effect on osteosarcoma cells is yet unknown. The aims of this study were to evaluate the effects of galangin on the proliferation, apoptosis, migration, and invasion of osteosarcoma cells and to explore the underlying mechanisms. We found that the proliferation of MG63 and U20S osteosarcoma cells decreased significantly, while the apoptosis of MG63 cells accelerated significantly after exposure to galangin. In addition, the migration and invasion of MG63 cells were significantly inhibited by galangin. Moreover, phosphoinositide 3-kinase (PI3K) and Aktp-Thr308 expression levels were found to be significantly lower in galangin-treated MG63 cells than in the control cells, and the protein expression levels of their downstream regulators cyclin D1 and matrix metalloproteinase 2/9 were also downregulated in galangin-treated groups, while those of p27Kip1, caspase-3, and caspase-8 were upregulated. These findings suggest that galangin suppresses osteosarcoma cells by inhibiting their proliferation and invasion and accelerating their apoptosis, and the mechanism may be associated with the inhibition of PI3K and its downstream signaling pathway.
Introduction
It is well known that the presence of Helicobacter pylori in the stomach induces gastritis and causes an immune response. Exposure of gastric epithelial cell lines to this germ induces the secretion of interleukin-8 (IL-8), which is a potent PMN-activating chemotactic cytokine. Interleukin-8 is usually elevated in gastric biopsy samples of patients with H. pylori-associated gastritis and significantly increases in the supernatant of in vitro cultivated biopsy samples of gastric mucosa with active H. pylori gastritis. Interleukin-8 is an activating factor for leucocytes and other pro-inflammatory factors, free radicals, and proteolytic enzymes. That is why natural compounds potentially useful in therapy are still investigated – among them flavonoids. They reveal anti-oxidative and anti-inflammatory activities and significantly inhibit the gastric mucosa damage.
The aim of the study
Was the estimation of the anti-inflammatory effects of flavonoids on H. pylori-induced activation of human gastric adenocarcinoma cells (AGS). After infection of AGS cells by cag PAI (+) H. pylori in vitro, secretion of IL-8, effects of flavonoids on viability of AGS cells, and effects of flavonoids on increase of H. pylori were determined. Such flavones as chrysin, quercetin, kaemferide, flavanone, galangin, and kaempferol were examined.
Results
This study has shown an inhibitory effect of flavonoids on the release of IL-8 through infected AGS cells (except chrysin), and no toxic effects to AGS cells were observed. Galangin revealed antibacterial effects against H. pylori. Flavonoids limit the inflammatory process through the inhibition of IL-8 release in infected AGS cells with H. pylori. The strongest inhibitor of IL-8 was galangin.
Galangin suppresses proliferation and induces apoptosis and autophagy in hepatocellular carcinoma (HCC) cells, but the precise mechanism is not clear. In this study, we demonstrated that galangin induced autophagy, enhanced the binding of SIRT1-LC3 and reduced the acetylation of endogenous LC3 in HepG2 cells. But this autophagy was inhibited by inactivation of SIRT1 meanwhile, galangin failed to reduce the acetylation of endogenous LC3 after SIRT1 was knocked-down. Collectively, these findings demonstrate a new mechanism by which galangin induces autophagy via the deacetylation of endogenous LC3 by SIRT1.
Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786‑0 and Caki‑1 cells was suppressed following exposure to various doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E‑cadherin and decreased expression levels of N‑cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose‑dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis.
Galangin, bioflavonoids, has been shown anti-cancer properties in various cancer cells. In this study, we investigated whether galangin could enhance TRAIL-mediated apoptosis in TRAIL resistant renal carcinoma Caki cells. Galangin alone and TRAIL alone had no effect on apoptosis, while combined treatment with galangin and TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498) but not normal cells (normal mouse kidney cells and human normal mesangial cells). Galangin induced down-regulation of Bcl-2 protein at the transcriptional level via inhibition of NF-? B activation but not p53 pathway. Furthermore, galangin induced down-regulation of cFLIP, Mcl-1 and survivin expression at the post-translational levels, and the over-expression of Bcl-2, cFLIP, Mcl-1 and survivin markedly reduced galangin-induced TRAIL sensitization. In addition, galangin increased proteasome activity, but galangin had no effect on expression of proteasome subunits (PSMA5 and PSMD4). In conclusion, our investigation suggests that galangin is a potent candidate for sensitizer of TRAIL resistant cancer cell therapy.
Microenvironmental regulation has become a promising strategy for complex disease treatment. The neurovascular unit (NVU), as the key structural basis to maintain an optimal brain microenvironment, has emerged as a new paradigm to understand the pathology of stroke. In this study, we investigated the effects of galangin, a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, on NVU microenvironment improvement and associated signal pathways in rats impaired by middle cerebral artery occlusion (MCAO). Galangin ameliorated neurological scores, cerebral infarct volume and cerebral edema and reduced the concentration of Evans blue (EB) in brain tissue. NVU ultrastructural changes were also improved by galangin. RT-PCR and western blot revealed that galangin protected NVUs through the Wnt/β-catenin pathway coupled with HIF-1α and vascular endothelial growth factor (VEGF). VEGF and β-catenin could be the key nodes of these two coupled pathways. In conclusion, Galangin might function as an anti-ischemic stroke drug by improving the microenvironment of NVUs.
Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources) induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure-activity relationship of myricetin (MN), fisetin (FN), quercetin (QN), kaempferol (KL) and galangin (GN). Using single cell alkaline gel electrophoresis (comet assay), we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids.
Acetaminophen (APAP) overdose causes severe liver and kidney damage. APAP-induced liver injury (AILI) represents the most frequent cause of drug-induced liver failure. APAP is relatively insoluble and can only be taken orally; however, its prodrug, propacetamol, is water soluble and usually injected directly. In this study, we examined the time-dependent effects of AILI after propacetamol injection in mice. After analyses of alanine aminotransferase and aspartate aminotransferase activities and liver histopathology, we demonstrated that a novel AILI mouse model can be established by single propacetamol injection. Furthermore, we compared the protective and therapeutic effects of galangin with a known liver protective extract, silymarin, and the only clinical agent for treating APAP toxicity, N-acetylcysteine (NAC), at the same dose in the model mice. We observed that galangin and silymarin were more effective than NAC for protecting against AILI. However, only NAC greatly improved both the survival time and rate consequent to a lethal dose of propacetamol. To decipher the hepatic protective mechanism(s) of galangin, galangin pretreatment significantly decreased the hepatic oxidative stress, increased hepatic glutathione level, and decreased hepatic microsomal CYP2E1 levels induced by propacetamol injection. In addition, propacetamol injection also reproduced the probability of APAP-induced kidney injury (AIKI), appearing similar to a clinical APAP overdose. Only galangin pretreatment showed the protective effect of AIKI. Thus, we have established a novel mouse model for AILI and AIKI using a single propacetamol injection. We also demonstrated that galangin provides significant protection against AILI and AIKI in this mouse model.
Retinoblastoma is a rare cancer of the infant retina that is diagnosed in approximately 8,000 children each year worldwide. It forms when both retinoblastoma gene (RB1) alleles are mutated in a susceptible retinal cell, probably a cone photoreceptor precursor. Loss of the tumour-suppressive functions of the retinoblastoma protein (pRB) leads to uncontrolled cell division and recurrent genomic changes during tumour progression. Although pRB is expressed in almost all tissues, cone precursors have biochemical and molecular features that may sensitize them to RB1 loss and enable tumorigenesis. Patient survival is >95% in high-income countries but <30% globally. However, outcomes are improving owing to increased disease awareness for earlier diagnosis, application of new guidelines and sharing of expertise. Intra-arterial and intravitreal chemotherapy have emerged as promising methods to salvage eyes that with conventional treatment might have been lost. Ongoing international collaborations will replace the multiple different classifications of eye involvement with standardized definitions to consistently assess the eligibility, efficacy and safety of treatment options. Life-long follow-up is warranted, as survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB1 loss in diverse tissues may open new avenues for treatment and prevention of retinoblastoma, as well as second cancers, in patients with germline RB1 mutations.
The high prevalence of age-related diseases among the population explosion of senior citizens has gained significance in the pursuit of therapeutic agents capable of slowing the progression of degenerative disorders and preventing premature ageing. Since our societies’ rising longevity is correlated with an increase in morbidity, preserving health in old age has become the main objective for biomedicine. Natural antioxidants are increasingly used as healthy ingredients in the nutrition, cosmetics, and pharmaceutical industries. Some synthetic drugs used as health supplements are enzyme inhibitors mediating several disease processes. However, due to concerns regarding their toxicity and adverse effects, several newly discovered heterogeneous phenolic and biphenolic structures have sparked a search for novel, safe, and effective agents, especially from natural sources. Natural antioxidants are one of the most well-studied natural product groups due to the wide range of biological effects they have. This review summarizes current knowledge on the various antioxidants and their action against age-related diseases like rheumatoid arthritis, skin ageing, eye degeneration, metabolic syndrome, and neuroinflammation. According to our study, a wide variety of antioxidants have been examined, and although some potential therapeutic molecules have been identified based on their antioxidant action, further in vivo studies and evaluation are needed before a possible therapeutic implementation as drug candidates.
The incidences of diabetes mellitus and other metabolic diseases are increasing worldwide. However, the current treatments for diabetes mellitus and other metabolic diseases are far from being clearly understood. Berberis species from the Barberry family, Berberidaceae, better known as Barberries are widely distributed worldwide. Several extracts and compounds obtained from Berberis species, particularly berberine, revealed effectiveness in the treatment of diabetes mellitus and other metabolic diseases. In the present study, a systematic search in the literature was performed to provide animal and clinical evidences regarding the therapeutic effects of berberine in metabolic diseases and diabetes mellitus. Also, its possible mechanism of action is described, in addition to the reported complication for berberine use and its drug interactions.Graphical abstract
Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B and C and alcoholic and nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, adaptive immune cells, such as CD8+ T cells, Th17 cells, and B cells, can also stimulate HCC development. Thus, the role of the hepatic immune system in HCC development is a highly complex topic. This review highlights the role of cytokine signals, NF-κB, JNK, innate and adaptive immunity, and hepatic stellate cells in HCC and discusses whether these pathways could be therapeutic targets. The authors will also discuss cholangiocarcinoma and liver metastasis because biliary inflammation and tumor-associated stroma are essential for cholangiocarcinoma development and because primary tumor-derived inflammatory mediators promote the formation of a “premetastasis niche” in the liver.
Purpose:
Galangin is an important flavonoid that has been reported to be of immense pharmacological importance. It has been shown to have a number of bioactivities which range from anticancer to antimicrobial. In this study the effects of Galangin were studied on the proliferation of the A498 kidney cancer cells.
Methods:
The antiproliferative effects were tested by MTT assay. Apoptosis was checked by subjecting the A498 cell to DAPI and annexin V/PI double staining. The effect on the cell migration and invasion was assessed by Boyden chamber assays. The expression of the apoptosis-related proteins was examined by western blot analysis.
Results:
Galangin inhibited the proliferation of the kidney cancer A498 cells. The IC50 of Galangin against the A498 cancer cells was 15 μM. The anticancer effects of Galangin were due to induction of apoptosis in the A498 cancer cells as indicated by DAPI and annexin V/PI staining. Furthermore, Galangin could increase the expression of Bax, Cyt-c and decrease the expression of Bcl-2. Galangin could also inhibit the migration and invasion of the kidney cancer cells and also suppress the expression of some of the important proteins of the PI3K/AKT/mTOR signalling pathway.
Conclusion:
In conclusion, Galangin could prove a useful new molecule in the treatment of kidney carcinoma.
Background/aim:
Anti-cancer activity of 3,5,7-trihydroxyflavone (galangin) has been documented in a variety of cancer types; however, its effect on human nasopharyngeal carcinoma (NPC) cells remains undetermined.
Materials and methods:
Human NPC cell lines were treated with galangin. Apoptosis was analyzed by assessing nuclear condensation, cleavage of pro-caspase-3 and poly ADP-ribose polymerase (PARP), and DNA fragmentation. Short hairpin RNA-mediated silencing of p53 was used for characterizing the role of p53 in the anti-cancer activity of galangin. Phosphatidylinositol 3-kinase (PI3K) inhibitor, protein kinase B (AKT) inhibitor, and ectopic expression of wild type p85α or p85α mutant lacking p110α-binding ability were utilized to confirm the involvement of PI3K/AKT inactivation in galangin-induced apoptosis.
Results:
Galangin induces apoptosis and S-phase arrest by attenuating the PI3K/AKT signaling pathway. Silencing of p53 did not block the anti-cancer activity of galangin on NPC cells.
Conclusion:
Galangin effects on apoptosis and S-phase arrest in NPC cells are mediated via interfering with the PI3K-AKT signaling pathway in a p53-independent manner.
Background:
Guidelines are important to standardize treatments and optimize outcomes. Several societies have published authoritative guidelines for patients with colon cancer, and a certain degree of variation can be predicted.
Objective:
This study aims to compare Western and Asian guidelines for the management of colon cancer.
Data sources:
A literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies published between 2010 and 2017 by the online resources from the official Web sites of the societies/panels. Sources included guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network.
Study selection:
Only full-text studies and the latest guidelines dealing with colon cancer were included. Studies and guidelines were separately assessed by 2 authors, who independently identified discrepancies and areas for further research. These were discussed and agreed with by all the authors.
Main outcome measures:
The recommendations of the guidelines of each society were compared, seeking discrepancies and potential areas for improvement.
Results:
Endoscopic techniques for the management of early colon cancer are discussed in detail in the Asian guidelines. Asian guidelines advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in selected T2 patients, whereas such an approach is still under investigation in Western countries. Only US guidelines describe neoadjuvant chemotherapy and radiotherapy. All the guidelines recommend adjuvant treatment in selected stage II patients, but agreement exists that this is performed without solid evidence, because better outcomes are hypothesized based on studies including stage III or stage II/III patients. The role of cytoreductive surgery with intra-abdominal chemotherapy is dubious, and European guidelines only recommend it in the setting of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal disease. Only US guidelines include a patient advocate in the drafting panel.
Limitations:
Bias may have arisen from country-specific socioeconomic and cultural issues, and from the latest available updates.
Conclusions:
Surgical approaches to colon cancer differ significantly among Western and Asian guidelines, reflecting different concepts of treatment. The role of adjuvant treatment in node-negative disease and quality-of-life assessment need further research.
Retinoblastoma is reported as a rare cancer that occurs during childhood. Although several treatments are available for retinoblastoma, there is a need for alternative new treatment modalities for retinoblastoma with better safety and efficacy profile. Galangin (3,5,7-trihydroxyflavone), is a flavonoid compound, which is found in high concentration in lesser galangal. Galangin has been reported to have various bioactivities, including anti-inflammation, anti-oxidative stress and anti-cancer through various pathways. The objective of our study was to explore the effects of galangin on the suppression of retinoblastoma in vitro and in vivo. Using MTT analysis, transwell-chamber migration analysis, colony-forming analysis, wound healing analysis, immunofluorescent assay of KI-67, we found that galangin exhibited a suppressive effect on human retinoblastoma cell proliferation and migration. Moreover, PTEN, a tumor-suppressor, was increased by galangin in cancer cells and in tumor tissues isolated from retinoblastoma xenograft models. Additionally, galangin reduced protein kinase B (Akt) phosphorylation, which was associated with PTEN up-regulation. Galangin-reduced Akt activation and cell proliferation was abolished by PTEN knockdown, which might be associated with the over-expression of phosphatidylinositol-3,4,5-triphosphate (PIP3)/diphosphate product (PIP2). Furthermore, flow cytometry, Hoechst 33258 staining and western blot assays indicated that galangin could induce apoptosis through promoting Caspase-3 pathway, which was, at least partly, dependent on PTEN expression. Our data illustrated that galangin treatment suppressed the growth of retinoblastoma tumor in vivo by anti-proliferative and apoptogenic mechanisms. Thus, galangin might be a safe and promising non-chemotherapeutic drug, which could be useful as an adjuvant against retinoblastoma.
The present study was designed to understand the anticancer property and molecular mechanisms associated with chemo preventive effects of galangin. The anticancer effect was evaluated in vitro using human cervical cancer cell line (HeLa). Galangin was found to be effective in inducing cell death and inhibiting proliferation & migration significantly. The inhibitory effect of galangin could be correlated with the increase in ROS production & induction of apoptosis. Besides this the activity of glyoxalase-1, an enzyme important for the detoxification of cytotoxic metabolite methy glyoxal and Nrf-2 (a trascription factor), involved in redox signalling was also found to be decreased. We concluded that galangin exerts its chemo preventive effect via redox signalling by inhibiting glyoxalase-1 & increasing oxidative & carbonyl stress.
Lung cancer represents a significant problem for public health worldwide. Galangin (GG), a natural active compound 3, 5, 7-trihydroxyflavone, is a type of bioflavonoid, which is isolated from the Alpinia galangal root and suggested to induce apoptosis in various cancers. We investigated the ability of Galangin (GG) to attenuate the drug resistance of human lung cancer cells, resistant to treatment of cisplatin (DDP). DDP is a pyrimidine analog, widely used in cancer treatment. Galangin and DDP co-treatment resulted in a dose-dependent suppression of the cell proliferation. Decreasing of p-STAT3 was included in p65 suppression by GG with DDP in combination. Additionally, the presence of GG potentiated the effects of DDP on apoptosis induction through suppressing Bcl-2 in DDP-resistant lung cancer cells. The pro-apoptotic proteins of Bax and Bid were up-regulated, accompanied with Caspases cleavage, leading to apoptosis. Moreover, in mice xenograft models, the combined therapy inhibited tumor growth compared to the GG or DDP treatment alone. Our data indicated a novel therapeutic strategy to potentiate DDP-induced anti-tumor effect in lung cancer cells with DDP resistance by GG through inactivating p-STAT3/p65 and Bcl-2 pathways.
Galangin (3,5,7‑trihydroxyflavone), is a natural flavonoid present in plants. Galangin is reported to exhibit anti‑cancer properties against various cancer types. The aim of the present study was to display the effects of galangin on glioma and its mechanism of action in A172 human glioma cancer cells. The results clearly indicated that treatment of galangin inhibited A172 cell migration and invasion under non‑toxic doses. A human proteinase array assay was conducted to elucidate the potential effects of galangin, and the obtained results demonstrated that treatment of galangin inhibited ADAM9 protein expression and mRNA expression, that are known to contribute to cancer progression. Sustained extracellular signal‑regulated kinase (Erk)1/2 activation was also monitored, which contributed to ADAM9 protein expression and mRNA inhibition as investigated using western blotting analysis and reverse transcription‑quantitative polymerase chain reaction experiment. Erk1/2 inhibition by inhibitor or small interfering (si)Erk transfection markedly terminated galangin‑inhibited A172 migration and invasion via an Erk1/2 activation mechanism. Collective results suggested that galangin may act as an effective chemotherapeutic agent for glioma cancer depending on its ability to bring about ADAM9 and Erk1/2 activation.
Hepatocellular carcinoma (HCC) is the sixth most common cancer. The Warburg effect is an important way by which HCC adapts to a hypoxic environment. The aim of the present study was to determine whether and how galangin reverses the Warburg effect in HCC cells. We treated three HCC cell lines, HepG2, Hep3B and PLC/PRF/5 with galangin for 24h, respectively. Cell proliferation was measured with MTT assay. Glucose uptake, lactate production and the oxygen consumption were measured. Pyruvate kinase activities were detected by measuring the consumption of NADH, and glycolytic pathway-related proteins were measured by Western blotting. The results showed that galangin suppressed proliferation of HCC cells, decreased glucose absorption and lactate production of HCC. In addition, galangin also gave rise to increased oxygen consumption in all three HCC cell lines. After treatment with galangin, the activity of pyruvate kinase was up-regulated and the expression levels of glycolytic pathway-related proteins were changed. These results suggest that galangin suppresses the Warburg effect in HCC cells, indicating that galangin might be a potential therapeutic agent for HCC.
Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are commonly experienced symptoms that share psychological and physical manifestations. One or more of these symptoms will affect nearly all patients at some point during their course of treatment or survivorship. These side effects are burdensome and reduce patients' quality of life well beyond their cancer diagnosis and associated care treatments. Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are likely to have multiple etiologies that make it difficult to identify the most effective method to manage them. In this review, we summarized the information on cancer-related fatigue, insomnia, and cancer-related cognitive impairment incidence and prevalence among breast cancer patients and survivors as well as recent research findings on pharmaceutical, psychological, and exercise interventions that have shown effectiveness in the treatment of these side effects. Our review revealed that most current pharmaceutical interventions tend to ameliorate symptoms only temporarily without addressing the underlying causes. Exercise and behavioral interventions are consistently more effective at managing chronic symptoms and possibly address an underlying etiology. Future research is needed to investigate effective interventions that can be delivered directly in clinic to a large portion of patients and survivors.
Natural flavonoids are proven to be powerful against various cancers, but few studies have investigated the potential effects of two flavonoids galangin and quercetin on a human gastric cancer cell line (SGC-7901). In vitro growth inhibition and apoptosis of the two flavonoids on the SGC-7901 cells as well as potential mechanism about apoptosis induction are reported in the present study. The assaying results showed that the two flavonoids at 40-200 μmol/L for 24-72 hours conferred lower cell viability of 14.1-90.3% in dose-And time-dependent manner, and at 160 μmol/L for 24-48 hours enhanced the proportion of apoptotic cells into 13.3-27.4% and 40.6-65.6%, respectively. Galangin was more powerful than quercetin to inhibit cell growth, induce apoptosis and decrease mitochondrial membrane potential (MMP). Oligonucleotide micro array, real-Time RT-PCR and Western-blot analyses revealed expression changes of the genes and proteins in the treated cells, clarifying a mechanism related to apoptosis induction. The two flavonoids activated caspase-8, which cleaved Bid into tBid; simultaneously, Bax transferred from cytosol into mitochondria to decrease MMP; consequentially, cytochrome c released from mitochondria activated caspase-9, and then caspase-9 activated caspase-3, which executed the apoptosis. That is, the apoptosis occurred via a mitochondrial pathway involving caspase-8/Bid/Bax activation.
Cancer is the second leading cause of death worldwide behind cardiovascular disease (1). According to the Global Burden of Disease (GBD) 2015 Study, which was conducted as part of a comprehensive regional and global research program assessing the mortality and disability caused by major diseases, injuries, and risk factors and involving over 500 researchers representing over 300 institutions and 50 countries, cancer mortality decreased between 2005 and 2015 despite the global incidence rates of cancer increasing during this period (1).
Osteosarcoma is the most common primary malignancy of the musculoskeletal system, and is associated with excessive proliferation and poor differentiation of osteoblasts. Currently, despite the use of traditional chemotherapy and radiotherapy, no satisfactory and effective agent has been developed to treat the disease. Herein, we found that a flavonoid natural product, galangin, could significantly attenuate human osteosarcoma cells proliferation, without causing obvious cell apoptosis. Moreover, galangin enhanced the expression of osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin and osteopontin) remarkably and elevated the alkaline phosphatase activity in human osteosarcoma cells. And galangin could also attenuated osteosarcoma growth in vivo.
These bioactivities of galangin resulted from its selective activation of the transforming growth factor (TGF)-β1/Smad2/3 signaling pathway, which was demonstrated by pathway blocking experiments. These findings suggested that galangin could be a promising agent to treat osteosarcoma. In addition, targeting TGF-β1 to induce osteogenic differentiation might represent a novel therapeutic strategy to treat osteosarcoma with minimal side effects.
Breast cancer is reported as the most frequent tumor with limited treatments among the female worldwide. Galangin, a natural active compound 3, 5, 7-trihydroxyflavone, is a type of bioflavonoid isolated from the Alpinia galangal root and suggested to induce apoptosis in various cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective anti-tumor agent for human breast cancer. Promoted expression of CHOP, a down-streaming transcription factor for endoplasmic reticulum stress (ER stress), enhanced death factor 4 (DR4) activity and accelerated reactive oxygen species (ROS) as well as cell death. Adenosine monophosphate-activated protein kinase (AMPK) is crucial for various cancers mortality. In the present study, galangin regulated ER stress to augment CHOP and DR4 expression levels, sensitizing TRAIL activity, leading to human breast cancer cell apoptosis through Caspase-3 activation, which was associated with AMPK phosphorylation. In addition, AMPK inhibition and silence reduced anti-cancer activity of galangin and TRAIL in combinational treatment. Hence, our study indicated that galangin could effectively stimulate human breast cancer cells to TRAIL-induced apoptosis through TRAIL/Caspase-3/AMPK signaling pathway. AMPK signaling pathway activation by galangin might be of benefit for promoting the effects of TRAIL-regulated anti-tumor therapeutic strategy.
Galangin is an active pharmacological ingredient from propolis and Alpinia officinarum Hance, and has been reported to have anti-cancer and antioxidative properties. Berberine, a major component of Berberis vulgaris extract, exhibits potent anti-cancer activities through distinct molecular mechanisms. However, the anticancer effect of galangin in combination with berberine is still unknown. In the present study, we demonstrated that the combination of galangin with berberine synergistically resulted in cell growth inhibition, apoptosis and cell cycle arrest at G2/M phase with the increased intracellular reactive oxygen species (ROS) levels in oesophageal carcinoma cells. Pretreatment with ROS scavenger promoted the apoptosis dramatically induced by co-treatment with galangin and berberine. Treatment with galangin and berberine alone caused the decreased expressions of Wnt3a and β-catenin. Interestingly, combination of galangin with berberine could further suppress Wnt3a and β-catenin expression and induce apoptosis in cancer cells. Additionally, in nude mice with xenograft tumors, the combinational treatment of galangin and berberine significantly inhibited the tumor growth without obvious toxicity. Overall, galangin in combination with berberine presented outstanding synergistic anticancer role in vitro and in vivo, indicating that the beneficial combination of galangin and berberine might provide a promising treatment for patients with oesophageal carcinoma.
Colorectal cancer is a major public health problem, being the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. There is wide variation over time among the different geographic areas due to variable exposure to risk factors, introduction and uptake of screening as well as access to appropriate treatment services. Indeed, a large proportion of the disparities may be attributed to socioeconomic status. Although colorectal cancer continues to be a disease of the developed world, incidence rates have been rising in developing countries. Moreover, the global burden is expected to further increase due to the growth and aging of the population and because of the adoption of westernized behaviors and lifestyle. Colorectal cancer screening has been proven to greatly reduce mortality rates that have declined in many longstanding as well as newly economically developed countries. Statistics on colorectal cancer occurrence are essential to develop targeted strategies that could alleviate the burden of the disease. The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.
