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Ampelopsin induces autophagy in human glioma cells. (A) U251 and (B) A172 cells were pretreated with 20 μM z-VAD-fmk for 2 h and then cultured with Control or Ampelopsin for 24 h. The cell proliferation was then examined using MTT analysis. (C) U251 and A172 cells were treated with various concentrations of Ampelopsin for 24 h, and LC3B and p62 expressions were determined by western blot. (D) U251 and A172 cells incubated with or without Ampelopsin for 24 h were harvested for acridine orange (AO) staining. Representative images of acridine orange-stained cancer cells were captured via fluorescent microscopy and exhibited. Data are presented as mean ± S.E.M. of three independent experiments conducted in duplicate, ** P < 0.01, and *** P < 0.001 versus the Con group.
Source publication
Glioma is the most common form of malignant brain cancer with high mortality rate in human. Therefore, finding effective therapeutic strategy and revealing the underlying molecular mechanism is necessary. Ampelopsin (Amp), an effective component of the traditional Chinese herb of Ampelopsis grossedentata, is reported to have important biological pr...
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Context 1
... order to further verify the effects of apoptosis in Ampelopsininduced cell death, the cell proliferation was examined after z-VAD-fmk treatment. Importantly, we found that z-VAD-fmk produced a partial down-regulation in the Ampelopsin-induced cell death, indicating that there might be other mechanism regarding to cell death induction ( Fig. 6A and B). Next, LC3B and p62 expression levels were assessed using western blot analysis. Fig. 6C indicated that Ampelopsin dosedependently promoted LC3B-II expression, as well as p62 levels, in both two glioma cell lines. Ampelopsin also resulted in the accumulation of bright red acidic esicles, which resembles autolysosomes through acridine ...
Context 2
... cell proliferation was examined after z-VAD-fmk treatment. Importantly, we found that z-VAD-fmk produced a partial down-regulation in the Ampelopsin-induced cell death, indicating that there might be other mechanism regarding to cell death induction ( Fig. 6A and B). Next, LC3B and p62 expression levels were assessed using western blot analysis. Fig. 6C indicated that Ampelopsin dosedependently promoted LC3B-II expression, as well as p62 levels, in both two glioma cell lines. Ampelopsin also resulted in the accumulation of bright red acidic esicles, which resembles autolysosomes through acridine orange staining (Fig. 6D). In conclusion, the findings here suggested that Ampelopsin ...
Context 3
... LC3B and p62 expression levels were assessed using western blot analysis. Fig. 6C indicated that Ampelopsin dosedependently promoted LC3B-II expression, as well as p62 levels, in both two glioma cell lines. Ampelopsin also resulted in the accumulation of bright red acidic esicles, which resembles autolysosomes through acridine orange staining (Fig. 6D). In conclusion, the findings here suggested that Ampelopsin produced autopgagic cell death through modulating autophagic formation in human glioma ...
Citations
... 1A and 1B). Table 1 displays the Val and 5-FU IC 50 values for each GC cell. To determine whether Val has a toxic side effect on normal cells, four types of normal cells (IMR-90, 293T, THLE-2, and GES-1) viability was determined by CCK-8 assay. ...
... It is well known that tumor cells have higher levels of ROS than normal cells and that excessive ROS in tumor cells has a killing effect on tumor cells [46,47]. Studies have revealed that some natural drugs could exert antitumor effects by increasing ROS accumulation [48][49][50]. To verify whether Val induced ROS accumulation in AGS cells, we detected ROS levels and found that Val could increase ROS accumulation in AGS cells. ...
Background
Valtrate (Val) was extracted from the Valeriana jatamansi Jones plant, had good antitumor activity. However, its precise molecular mechanism in cancer cells was still unclear. This study investigated the effect of Val on gastric cancer (GC) cells and its potential molecular mechanism.
Methods
Cell viability was examined by CCK-8 assay. Cell cycle, apoptosis, and Reactive oxygen species (ROS) level were analyzed by flow cytometry. The migration effect of Val on AGS cells was analyzed by transwell and wound-healing assay. The expression levels of proteins were analyzed by western blot.
Results
The cell viability assay results demonstrated that Val significantly decreased GC cell viability. Apoptosis assay results revealed that Val induced mitochondria-dependent apoptosis through the Bad/Bcl-2/cyto-c/cle-casp-3/cle-PARP pathways. Further exploration found that Val induced apoptosis through increasing the expression of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and Inhibitor kappa B alpha (IκB-α) proteins and decreasing the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and nuclear factor kappa-B (NF-κB) proteins; these expression levels of proteins were reversed by mitogen-activated protein kinase (MAPK) inhibitor. Furthermore, Val induced G2/M phase arrest in AGS cells through downregulating the expression of phosphorylated protein kinase B (p-AKT). Moreover, Val induced inhibition of AGS cell migration through downregulating the expression of p-GSK-3β and β-catenin. In addition, Val promoted the ROS accumulation of AGS cells. Further investigation found that Val-induced apoptosis, arrested the cell cycle, and inhibited cell migration, and that its signaling pathways related to protein expressions were reversed by the ROS scavenger, N-acetyl-L-cysteine.
Conclusion
Val induced apoptosis, arrested the cell cycle, and inhibited migration by ROS-mediated MAPK/STAT3/NF-κB, AKT/Cyclin B/CDK1/2, and GSK-3β/β-catenin signaling pathways in AGS cells.
... Alkaloids from the Amaryllidaceae family inhibit the independent efects of p53 on the proliferation of colon cancer cells [12]. Phenolic compounds such as ampelopsin and apigenin through their antioxidant and anti-infammatory properties induce cell death by apoptosis, suppressing miR-512-3p and promoting the G1 phase of cell cycle involving the p27 Kip1 protein in glioma and breast cancer cells [13][14][15][16]. Other bioactive compounds like tomentosin, a terpenoid isolated from plants of the Asteraceae family such as Inula viscosa, and jolkinolide B (extracted from Euphorbia kansui) inhibit the proliferation and migratory activity of cancer cells by downregulating the PI3K-Akt pathway and the expression of certain proinfammatory genes [17][18][19]. ...
Te increasing prevalence of cancers and the multiple side efects of cancer treatments have led researchers to constantly search for plants containing bioactive compounds with cell death properties. Tis work aimed at evaluating the antiproliferative efect of an Acmella caulirhiza extract. After evaluation of the in vitro antioxidant potential of the three extracts of Acmella caulirhiza (aqueous (AE-Ac), hydroethanolic (HEE-Ac), and ethanolic (EE-Ac)) through the scavenging of DPPH • and NO • radicals, the extract with the best antioxidant activity was selected for bioactive compound assessment and antiproliferative tests. Subsequently, the cytotoxic activity was evaluated on the viability of breast (MCF-7), brain (CT2A, SB-28, and GL-261), colon (MC-38), and skin (YUMM 1.7 and B16-F1) cancer lines using the MTT method. Ten, the line where the extract was the most active was selected to evaluate the expression of certain genes involved in cancerogenesis by RT-PCR and the expression of cleaved caspase-3 involved in cell death mechanism by western blot. Te AE-Ac showed the best scavenging activity with IC 50 s of 0.52 and 0.02 for DPPH • and NO • , respectively. Tis AE-Ac was found to contain alkaloids, favonoids, and tannins and was more active on YUMM 1.7 cells (IC 50 = 149.42 and 31.99 μg/mL for 24 and 48 h, respectively). Results also showed that AE-Ac downregulated the expression of infammation (IL-1b (p � 0.017) and IL-6 (p � 0.028)), growth factors (PDGF (p � 0.039), IGF (p � 0.034), E 2 F 1 (p � 0.038), and E 2 F 2 (p � 0.016)), and antiapoptotic protein genes (Bcl-2 (p � 0.028) and Bcl-6 (p � 0.039)). Te cleaved caspase-3 was positively modulated by the AE-Ac inducing thus cell death by apoptosis. AE-Ac showed inhibitory efects on the expression of genes involved in cancer progression making it a potential health intervention agent that can be exploited in cancer therapy protocols.
... Xiang et al., 2019), anti-atherosclerosis (Yang et al., 2020), anti-inflammatory (Hou et al., 2015), anti-oxidative(Z. Guo, Guozhang, Wang, Li, & Liu, 2019) ,and anti-carcinogenic(B. Zhang et al., 2012) effects. ...
Recent studies demonstrated that dihydromyricetin (DHM) has prominent therapeutic effects on liver injury and liver cancer. By summarizing the current preclinical in vitro and in vivo studies, the present review examines the preventive and therapeutic effects of DHM in liver disorders as well as its potential mechanisms. Briefly, in both chemical- and alcohol-induced liver injury models, DHM ameliorates hepatocyte necrosis and steatosis while promoting liver regeneration. In addition, DHM can alleviate NAFLD via regulating lipid/glucose metabolism, probably due to its anti-inflammatory or sirtuins-dependent mechanisms. Furthermore, DHM treatment inhibits proliferation, induces apoptosis and autophagy, regulates redox balance in the liver cancer cells, thus exhibiting remarkable anti-cancer effects. With the accumulating interests in utilizing natural products to target common diseases, our work aims to improve the understanding of DHM acting as a novel treatment for liver diseases and to accelerate its translation.
... Previous phytochemical study of A. grossedentata mainly includes flavonoids, polyphenols, steroids, terpenes, and volatile components [1,2]. Furthermore, it has been discovered to have a wide range of biological activities, including antioxidant [3,4], liver protection [5,6], antidiabetic [7,8], antitumor [9,10], antiviral [11], anti-inflammatory [12], and antimicrobial [13] effects. ...
... Although about 40 compounds have been found in it, its biological activity has so far been attributed to its most abundant flavonoid, dihydromyricetin. Due to our efforts to search for natural products with novel structures and various biological activity [14,15], nineteen compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), including two new flavonoids named meichasu A-B (1-2) and seventeen other known compounds, were isolated from the alcoholic extract of A. grossedentata leaves in the present work ( Figure 1). Among them, nine compounds were isolated from A. grossedentata for the first time. ...
... Although about 40 compounds have been found in it, its biological activity has so far been a ributed to its most abundant flavonoid, dihydromyricetin. Due to our efforts to search for natural products with novel structures and various biological activity [14,15], nineteen compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), including two new flavonoids named meichasu A-B (1-2) and seventeen other known compounds, were isolated from the alcoholic extract of A. grossedentata leaves in the present work ( Figure 1). Among them, nine compounds were isolated from A. grossedentata for the first time. ...
Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1–2) and seventeen known compounds (3–19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure–activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 μM. In addition, compounds 1–2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.
... JNK activation is able to block the U251 cell cycle [22,23]; therefore, we next determined the expression levels of JNK and p-JNK proteins by Western blotting. Relative to the control group, MITC-12 treatment significantly increased the p-JNK:JNK ratio (Figure 6), suggesting that MITC-12 induces cell cycle arrest by regulating the expression of cell cycle-associated proteins, and that this function of MITC-12 is associated with JNK activation. ...
A major active constituent of Moringa oleifera Lam. is 4-[(α-L-rhamnose oxy) benzyl] isothiocyanate (MITC). To broaden MITC’s application and improve its biological activity, we synthesized a series of MITC quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma.
... Polyphyllin VII promotes apoptosis and autophagic cell death via ROS-inhibited AKT activity, and sensitizes glioma cells to temozolomide (45). Ampelopsin, an effective component of the traditional Chinese herb of Ampelopsis grossedentata, inhibits human glioma through inducing apoptosis and autophagy dependent on ROS generation and JNK pathway (46). Fucoxanthin, a natural carotenoid derived from algae, induces apoptosis in human glioma cells via triggering of ROS-mediated oxidative damage and regulation of MAPKs and PI3K-AKT pathways (47). ...
Gliomas are characterized by high morbidity and mortality, and have only slightly increased survival with recent considerable improvements for treatment. An innovative therapeutic strategy had been developed via inducing ROS-dependent cell death by targeting antioxidant proteins. In this study, we found that glioma tissues expressed high levels of superoxide dismutase 1 (SOD1). The expression of SOD1 was upregulated in glioma grade III and V tissues compared with that in normal brain tissues or glioma grade I tissues. U251 and U87 glioma cells expressed high levels of SOD1, low levels of SOD2 and very low levels of SOD3. LCS-1, an inhibitor of SOD1, increased the expression SOD1 at both mRNA and protein levels slightly but significantly. As expected, LCS-1 caused ROS production in a dose- and time-dependent manner. SOD1 inhibition also induced the gene expression of HO-1, GCLC, GCLM and NQO1 which are targeting genes of nuclear factor erythroid 2-related factor 2, suggesting the activation of ROS signal pathway. Importantly, LCS-1 induced death of U251 and U87 cells dose- and time-dependently. The cell death was reversed by the pretreatment of cells with ROS scavenges NAC or GSH. Furthermore, LCS-1 decreased the growth of xenograft tumors formed by U87 glioma cells in nude mice. Mechanistically, the inhibition of P53, caspases did not reverse LCS-1-induced cell death, indicating the failure of these molecules involving in cell death. Moreover, we found that LCS-1 treatment induced the degradation of both PARP and BRCA1 simultaneously, suggesting that LCS-1-induced cell death may be associated with the failure of DNA damage repair. Taking together, these results suggest that the degradation of both PARP and BRCA1 may contribute to cell death induced by SOD1 inhibition, and SOD1 may be a target for glioma therapy.
... 18 For example, Ampelopsin (Amp) has been shown to trigger apoptosis and autophagy-dependent cell death by promoting ROS generation and the activation of c-Jun Nterminal kinase (JNK) in glioma cells. 19 Galectin-1 is a member of the galactose lectin family with multiple biological activities. It is highly expressed in numerous tumors and regulates the proliferation, migration, and growth of tumor cells. ...
Regulated cell death (RCD), also well-known as programmed cell death (PCD), refers to the form of cell death that can be regulated by a variety of biomacromolecules, which is distinctive from accidental cell death (ACD). Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis, which may ultimately lead to the establishment of different potential therapeutic strategies. Hitherto, targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue, which has rapidly progressed in many types of human cancers. Thus, in this review, we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways, but the crucial pathways of other RCD subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis and lysosome-dependent cell death (LCD) in cancer. Moreover, we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment, such as single-target, dual or multiple-target small-molecule compounds, drug combinations, and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.
... [32][33] Interestingly, Ampelopsin, which is the bio-compound only found in R-AMR2.2 has been reported to suppress the glioma cell proliferation by modulating G1 and S phase arrest as well as inducing cell apoptosis. 34 Moreover, it previously proved that Ampelopsin has excellent capacity on oxidative stress and inflammation by reducing ROS accumulation, increasing cellular antioxidant defense through activation of the ERK, Akt, and NF-κ B signaling pathways. [35][36][37] Therefore, the activity of R-AMR on anti-oxidation might result from the ability of these bioactive compounds to scavenge free radicals and protect cells from the serious situation. ...
Aum-Ma-Rit recipe (R-AMR), a traditional Thai drug, has been recorded for treatment of GI disorders for several decades. It has been clinically applied as a complementary treatment for taking care of colon cancer patients. However, there are no scientific studies to confirm its traditional use. Therefore, this study was aimed to primarily screen biological properties of RAMR on anti-oxidation as well as anticancer against HT-29 human colon cancer. The recipe with and without tamarind as an aqueous adjuvant was extracted using two types of solvents, water and ethanol. Total phenolic and total flavonoid contents of all tested extracts were evaluated. LC-MS/MS was also performed. DPPH, ABTS, FRAP, and ORAC scavenging assays were used to measure an in vitro antioxidant activity and the property of extracts on killing HT-29 human colon cancer cells was investigated using MTT assay. The result revealed that all sample extracts were composed of a huge source of phenolic and flavonoid. RAMR2.2 possessed an intense antioxidant property against DPPH (17.45 ± 0.3 µg/ml), ABTS (4.04 ±0.01 µg/ml), FRAP (6859.26 ± 0.00 µM of FeSO4 equivalent/mg of extract), ORAC (334.06 ± 18.52 µM of trolox equivalent/mg of extract), and also inhibiting lipid peroxidation (88.78 ± 1.11 %). MTT assay revealed that extracts have no cytotoxic effects on HT-29 human colon cancer cells. R-AMR had a strong ability on anti-oxidation even if it had less cytotoxic effects on HT-29. Therefore, the current study exhibited that the recipe may act as a chemopreventive agent for taking care of cancer patients.
... Anti-glioma role of ampelopsin was reported in human glioma (U251 and A172) cell lines (treated at 0, 25, 50, and 100 μM for 24 h) and human glioma xenograft models (50 and 100 mg/kg). Ampelopsin exerted its anti-glioma effects both through intrinsic and extrinsic pathways and upregulated c-Jun N-terminal protein kinase (JNK) expression [32]. In hepatoma HepG2 cells ampelopsin induces apoptosis through activating death receptor 4 and 5 mediated increase of Bax/Bcl-2 ratio. ...
... Differential regulation may be explained on the basis of ampelopsin regulation of cyclins and CDK's [59]. Moreover, ampelopsin-treated U251 and A172 glioma cells were observed to be arrested in G1 and S phase initiated through ROS generation and autophagy [32]. It has also been suggested that ampelopsin may induce tubulin polymerization in lung adeno carcinoma SPC-A-1 cell line which may subsequently disrupt mitosis and arrest cells in S-phase both in SPC-A-1 and Hela cells [35,43]. ...
Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical.
... 11 Previous phytochemical investigations on this plant reported the presence of various types of meroterpenoids and flavonoids, 11,12 some of which exhibited cytotoxic, antioxidant, anti-inflammatory, anti-fatigue, and anti-cancer, 12 antitumor, antibacterial, antiviral, and antiobesity effects. [11][12][13][14] In this study, the spray drying technique was applied to process a hydroalcoholic extract from the aerial parts of A. cantoniensis and ampelopsin content, physicochemical properties, and anti-ulcer potential were evaluated. monitored by TLC. ...
