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Effect of the combined treatment of Rg3 and 5-FU on the apoptosis of colon cancer cells in vitro. (A) The percentage of apoptotic SW620 and LOVO cells in the different groups. (B) Apoptosis-related proteins [(cleaved (Cl)-caspase 9, Cl-caspase 3 and Apaf-1] were assessed by western blot analysis in SW620 and LOVO cells. Three independent repetitions for each experiment were carried out. *** P<0.001, compared with the Rg3+5-FU group. 5-FU, 5-fluorouracil; Rg3, ginsenoside Rg3; Apaf-1, Apoptotic protease activating factor 1.
Source publication
Chemotherapy is one of the most commonly used treatments for patients with advanced colon cancer, yet the toxicity of chemotherapy agents, such as 5‑fluorouracil (5‑FU), limits the effectiveness of chemotherapy. Ginsenoside Rg3 (Rg3) is an active ingredient isolated from ginseng. Rg3 has been shown to display anticancer effects on a variety of mali...
Contexts in source publication
Context 1
... treatment of Rg3 and 5-FU promotes apoptosis of colon cancer cells. Fist, we found that the apoptosis of the colon cancer cells treated with Rg3 combined with 5-FU was significantly higher than that of Rg3 or 5-FU alone (Fig. 3A). The levels of apoptosis-related proteins in the SW620 and LOVO cells were assessed by western blot analysis. As shown in Fig. 3B, expression levels of Apaf-1, cleaved (Cl)-caspase 9 and Cl-caspase 3 protein in colon cancer cells (SW620 and LOVO) treated with Rg3 were significantly increased, and the expression of these ...
Context 2
... of Rg3 and 5-FU promotes apoptosis of colon cancer cells. Fist, we found that the apoptosis of the colon cancer cells treated with Rg3 combined with 5-FU was significantly higher than that of Rg3 or 5-FU alone (Fig. 3A). The levels of apoptosis-related proteins in the SW620 and LOVO cells were assessed by western blot analysis. As shown in Fig. 3B, expression levels of Apaf-1, cleaved (Cl)-caspase 9 and Cl-caspase 3 protein in colon cancer cells (SW620 and LOVO) treated with Rg3 were significantly increased, and the expression of these apoptosis-related protein in colon cancer cells following 5-FU treatment was significantly higher than that treated with Rg3. More importantly, ...
Citations
... CDK4 and CDK2, both members of the serine/ threonine kinase family, primarily affect the G1 to S phase transition of the cell cycle (Lamb et al., 2003). Notably, in PI3K/ AKT pathway-activated CRC cells, CDK2 and CDK4 upregulation reportedly promotes apoptosis (Hong et al., 2020), underscoring the intricate interactions between signaling pathways and cell cycle regulation in CRC. Furthermore, CHEK1 responds to DNA damage in CRC cells and TP53 status influences its function (Gali-Muhtasib et al., 2008). ...
Background: Ailanthone, a small compound derived from the bark of Ailanthus altissima (Mill.) Swingle, has several anti-tumour properties. However, the activity and mechanism of ailanthone in colorectal cancer (CRC) remain to be investigated. This study aims to comprehensively investigate the mechanism of ailanthone in the treatment of CRC by employing a combination of network pharmacology, bioinformatics analysis, and molecular biological technique.
Methods: The druggability of ailanthone was examined, and its targets were identified using relevant databases. The RNA sequencing data of individuals with CRC obtained from the Cancer Genome Atlas (TCGA) database were analyzed. Utilizing the R programming language, an in-depth investigation of differentially expressed genes was carried out, and the potential target of ailanthone for anti-CRC was found. Through the integration of protein-protein interaction (PPI) network analysis, GO and KEGG enrichment studies to search for the key pathway of the action of Ailanthone. Then, by employing molecular docking verification, flow cytometry, Transwell assays, and Immunofluorescence to corroborate these discoveries.
Results: Data regarding pharmacokinetic parameters and 137 target genes for ailanthone were obtained. Leveraging The Cancer Genome Atlas database, information regarding 2,551 differentially expressed genes was extracted. Subsequent analyses, encompassing protein–protein interaction network analysis, survival analysis, functional enrichment analysis, and molecular docking verification, revealed the PI3K/AKT signaling pathway as pivotal mediators of ailanthone against CRC. Additionally, the in vitro experiments indicated that ailanthone substantially affects the cell cycle, induces apoptosis in CRC cells (HCT116 and SW620 cells), and impedes the migration and invasion capabilities of these cells. Immunofluorescence staining showed that ailanthone significantly inhibited the phosphorylation of AKT protein and suppressed the activation of the PI3K/AKT signaling pathway, thereby inhibiting the proliferation and metastasis of CRC cells.
Conclusion: Therefore, our findings indicate that Ailanthone exerts anti-CRC effects primarily by inhibiting the activation of the PI3K/AKT pathway. Additionally, we propose that Ailanthone holds potential as a therapeutic agent for the treatment of human CRC.
... Moreover, FTGs can antagonize the tumors through the above pathways. In addition, ginsenosides Rg3, CK, etc. can inhibit the proliferation of human colon cancer cells and thus exert anti-tumor effects [41,42]. This also lays the foundation for the subsequent clinical application of FTGs. ...
The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.
... a previous study reported that Bcaas induce cell cycle arrest, leading to apoptosis in hcc cells [55]. Furthermore, the inhibition of tumor cell proliferation can also be accomplished by inducing apoptosis in tumor cells [56]. ...
Background
We aimed to assess differences in intestinal microflora between patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) and those without MVI. Additionally, we investigated the potential of the microbiome as a non-invasive biomarker for patients with MVI.
Methods
We analyzed the preoperative gut microbiomes (GMs) of two groups, the MVI (n = 46) and non-MVI (n = 56) groups, using 16S ribosomal RNA gene sequencing data. At the operational taxonomic unit level, we employed random forest models to predict MVI risk and validated the results in independent validation cohorts [MVI group (n = 17) and non-MVI group (n = 15)].
Results
β diversity analysis, utilizing weighted UniFrac distances, revealed a significant difference between the MVI and non-MVI groups, as indicated by non-metric multidimensional scaling and principal coordinate analysis. We also observed a significant correlation between the characteristic intestinal microbial communities at the genus level and their main functions. Nine optimal microbial markers were identified, with an area under the curve of 79.76% between 46 MVI and 56 non-MVI samples and 79.80% in the independent verification group.
Conclusion
This pioneering analysis of the GM in patients with operable HBV-HCC with and without MVI opens new avenues for treating HBV-HCC with MVI. We successfully established a diagnostic model and independently verified microbial markers for patients with MVI. As preoperative targeted biomarkers, GM holds potential as a non-invasive tool for patients with HBV-HCC with MVI.
... For example, ginsenoside Rg3 was found to enhance the inhibitory effect of 5-fluorouracil (5-FU) in colon cancer by inhibiting the PI3K/AKT pathway. 20 Naringin was also shown to inhibit the growth of CRC cells by suppressing the PI3K/AKT/mammalian target of rapamycin (PI3K/ AKT/mTOR) pathway. 21 In addition, α-Cyperone suppresses cervical cancer cell proliferation by inhibiting PI3K/AKT/mTOR pathway. ...
... Ginsenoside Rg3 inhibits angiogenesis, induces tumor cell apoptosis, selectively inhibits tumor cell metastasis, and enhances immune function [10]. In addition, ginsenoside Rg3 can inhibit the proliferation, invasion, and migration of lung [11], gastric [12], prostate [13], colon [14], and pancreatic cancer cells [15]. There is growing evidence for the role of ginsenoside Rg3 in cancer prevention. ...
Although ginsenoside Rg3 has been shown to exert anticancer effects in various malignancies, the effects and molecular mechanisms of ginsenoside Rg3 in cervical cancer (CC) remain unclear. This study explored the effect of ginsenoside Rg3 on CC development at the cellular level. The effect of ginsenoside Rg3 on cell proliferation was measured using colony formation and Cell Counting Kit-8 assays. Migration, invasion, and in vitro angiogenesis of CC cells were detected using wound healing, transwell, and tube formation assays, respectively. In addition, we explored the target genes and molecular mechanisms of ginsenoside Rg3 in CC cells overexpressing AKT serine/threonine kinase 2 (AKT2). The results indicated that ginsenoside Rg3 suppressed proliferation, migration, invasion, and tube formation of CC cells in vitro. In addition, ginsenoside Rg3 treatment decreased the expression of AKT2 in CC cells. Moreover, ginsenoside Rg3 treatment partially reversed AKT2 overexpression-mediated reduction in cell proliferation, migration, invasion, and tube formation. In conclusion, the above findings suggested that ginsenoside Rg3 inhibits CC progression via regulation of AKT2 expression, which might provide a potential therapeutic target for tumor therapy.
... Alternatively, in vitro studies have concluded that Rg3 is responsible for suppression of angiogenesis, also contributing to its anti-tumour effects [96]. In addition, Rg3 inhibits cancer cell proliferation by downregulating Wnt/β-catenin and triggers tumour cell apoptosis by promoting various signaling pathways, including mitogen-induced and AMP-induced protein kinase pathways [97][98][99]. It is responsible for increasing sensitization of tumour cells to chemotherapy, as well [100,101]. ...
Despite the existence of extensive clinical research and novel therapeutic treatments, cancer remains undefeated and the significant cause of death worldwide. Cancer is a disease in which growth of cells goes out of control, being also able to invade other parts of the body. Cellular division is strictly controlled by multiple checkpoints like G1/S and G2/M which, when dysregulated, lead to uncontrollable cell division. The current remedies which are being utilized to combat cancer are monoclonal antibodies, chemotherapy, cryoablation, and bone marrow transplant etc. and these have also been greatly disheartening because of their serious adverse effects like hy-potension, neuropathy, necrosis, leukemia relapse and many more. Bioactive compounds derived from natural products have marked the history of the development of novel drug therapies against cancer among which ginsenosides have no peer as they target several signaling pathways, which when abnormally regulated, lead to cancer. Substantial research has reported that ginsenosides like Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2 etc. can prevent and treat cancer by targeting different pathways and molecules by induction of autophagy, neutralizing ROS, induction of cancerous cell death by controlling the p53 pathway, modulation of miRNAs by decreasing Smad2 expression, regulating Bcl-2 expression by normalizing the NF-Kb pathway, inhibition of inflammatory pathways by decreasing the production of cytokines like IL-8, causing cell cycle arrest by restricting cyclin E1 and CDC2, and induction of apoptosis during malignancy by decreasing β-catenin levels etc. In this review, we have analyzed the anti-cancer therapeutic potential of various ginsenoside compounds in order to consider their possible use in new strategies in the fight against cancer.
... 5-FU treatment is able to shrink the tumor mass of CC. But 5-FU was also toxic to normal cells, causing serious adverse reactions, which severely limited its clinical application 4 . Studies have shown that about 50% of CC patients treated with 5-FU develop resistance, which is the leading cause of poor prognosis in colon cancer patients 5 . ...
Background
Accumulating studies demonstrated that resistance of colon cancer (CC) to 5-fluorouracil (5-FU) contributes to adverse prognosis. We investigated how Kruppel-like factor 4 (KLF4) affected 5-FU resistance and autophagy in CC cells.
Methods
KLF4 expression and its downstream target gene RAB26 in CC tissues was analyzed by bioinformatics analysis, and the effect of abnormal KLF4 expression on prognoses of CC patients was predicted. Luciferase reporter assay detected the targeted relationship between KLF4 and RAB26. The viability and apoptosis of CC cells were analyzed by CCK-8 and flow cytometry. The formation of intracellular autophagosomes was detected by confocal laser scanning microscopy and immunofluorescence staining. The mRNA and protein levels were assayed by qRT-PCR and western blot. A xenograft animal model was constructed to verify the function of KLF4. Rescue assay was employed to verify whether KLF4/RAB26 could affect 5-FU resistance in CC cells through autophagy.
Results
KLF4 and RAB26 were lowly expressed in CC. KLF4 correlated with patients’ survival. KLF4 was down-regulated in 5-FU resistant CC cells. KLF4 overexpression suppressed the proliferation and 5-FU resistance of CC cells, and inhibited LC3 II/I expression and autophagosome formation. Autophagy activator Rapamycin or sh-RAB26 treatment reversed the impact of KLF4 overexpression on 5-FU resistance. In vivo assay verified that KLF4 inhibited 5-FU resistance in CC cells. Rescue experiments revealed that KLF4 targeted RAB26 to inhibit CC cell autophagy, resulting in decreasing the resistance to 5-FU.
Conclusion
KLF4 strengthened the sensitivity of CC cells to 5-FU by targeting RAB26 to restrain autophagy pathway.
... Therefore, the combination of Oxaliplatin and five-fluorouracil may exhibit some advantage in treatment. 24 However, additional researchers also considered a relatively unsatisfactory effect of chemotherapy alone. 25 In terms of the major causes, tumor cells may spread widely in patients with advanced colon cancer, leading to a higher risk of complications, poor overall resistance of the body and compromised immunity in these patients. ...
Objective:
To evaluate the clinical effect and safety of immunotherapy combined with chemotherapy in patients with advanced colon cancer.
Methods:
This is a retrospective study. The subjects of this study were 120 patients with advanced colon cancer who were admitted to The No.2 Hospital of Baoding from November 30, 2019 to November 30, 2021. The enrolled patients were randomly divided into two groups, with 60 cases in each group. Patients in the control group were given F0LF0X4 regimen, while those in the study group were provided with Bevacizumab therapy on the basis of the method in the control group. All patients were evaluated after two cycles of treatment. The comparison of outcome measures included the curative effects, adverse drug reactions, improvement of quality-of-life scores and changes in tumor markers between the two groups.
Results:
The total effective rate of the study group was significantly better than that of the control group. There was no significant difference in the incidence of adverse drug reactions between the two groups. After treatment, the study group had a significantly higher rate of improved quality of life score, while the obviously lower rate of the aggravated score than those in the control group. The levels of CEA, CA19-9 and CA125 in the study group were significantly lower than those in the control group after treatment.
Conclusion:
Targeted therapy combined with chemotherapy is a safe and effective therapeutic option that has a definite curative effect in the treatment of patients with advanced colon cancer.
... Previous studies have shown a remarkable anti-gastric cancer activity of components of ginseng, which induced tumor cell apoptosis via reactive oxygen species, promoted endoplasmic reticulum stress, and inhibited tumor cell migration and invasion [53][54][55]. In particular, when ingredients of ginseng are used in combination with 5-FU, they can significantly enhance the inhibition of colorectal [56,57], liver [58,59], pancreatic [60], and gastric [61] cancers. These synergistic anticancer effects imply that the combination of G-TMPs with FBC may have therapeutic use for the treatment of cancer. ...
Background:
Ginseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC.
Methods:
Eight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers.
Results:
A total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p < 0.00001) and disease control (RR = 1.13, 95% CI: 1.08 to 1.19, p < 0.00001) rates than those treated with FBC alone. Additionally, the combination group had a better QoL, higher proportions of CD3+ T cells, CD4+ T cells, and natural killer cells, as well as a higher CD4+/CD8+ T-cell ratio. Furthermore, lower levels of CA19-9, CA72-4, and CEA were confirmed in the combination treatment group. In addition, G-TMPs reduced the incidence of ADRs during chemotherapy.
Conclusion:
In combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted.
Systematic review registration:
PROSPERO Number: CRD42021264938.
... Hence, there is need to synthesize a new bioactive material since the existed compounds efficiency is reduced with the passage of time and this regard various techniques have been applied for the synthesis of organic compounds (Kousar et al., 2015, Khalafallah and Ahmed 2017, Ocheni and Clement 2017, Deeba et al., 2018, Abdellatif and Abd El Rady 2020, Amos-Tautua et al., 2020. 5-Fluorouracil (5-Fu), (Carrillo et al., 2015, Jubeen et al., 2018) was discovered half a century ago, persists to be extensively used in the cure of common malignancies involving colon cancer (Hong et al., 2020), breast (Su et al., 2020) brain (Shinde et al., 2020) and skin (de Oliveira et al., 2020). Even though 5-Fu is the better-quality chemotherapeutic agents for CRC (colorectal cancer) (Vodenkova et al., 2020), still it has some shortcomings that include fast metabolism, very short-term half-life, minimal bioavailability, cell mortality and insufficient selectivity for tumorous cells, all these drawbacks limit its efficacy in cancer chemotherapy (Krishnaiah et al., 2003, Entezar-Almahdi et al., 2020 and the response rate is reported only 10-15 % (Sethy and Kundu 2021). ...
Antibiotic residues in wastewater are considered lethal to the crops and aquatic life. One of the promising way to treat this kind of wastewater is the use of constructed wetlands coupled with microbial fuel cell (CW-MFC). In this treatment, bacterial action and redox operation occurs at anaerobic anode and aerobic cathode respectively. Four different configurations of CW-MFCs was applied for comparison. This study focusses on the investigation of the removal of Co-trimoxazole (CMX), other co-existing pollutants and furthermore, the generation of green electricity with low hydraulic retention time (HRT) was studied. Results revealed that the effluent from configuration 1 (gravel based) had lower (CMX) concentration. This removal performance may be associated to greater electrode absorption capacity for (CMX). The removal efficiency was 92.58% at HRT of 3d and effluent concentration was 4 mg/L. On the other hand, CW-MFC1 exhibited the BOD removal (60.60%) regardless of the increasing effluent antibiotic concentration. Pure strain of Geobactor sulfereducens, adjusted with anaerobic sludge increased the bio-film growth. Maximum power density of 480.2 mW/m−3 observed for CW-MFC1. Electricity generation characteristic were also found to be effected with HRT.
