Mechanism of gypenosides of Gynostemma pentaphyllum inducing apoptosis of renal cell carcinoma by PI3K/AKT/mTOR pathway

Liu, Hui; Li, Xiuming; Duan, Yu; Xie, Jinbo; Piao, Xiang‐Lan

doi:10.1016/j.jep.2021.113907

Cited by 46 publications

(29 citation statements)

References 31 publications

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“…After the GPS treatment, the level of intracellular ROS level was increased, and DNA fragmentation and apoptotic morphology were observed. Liu et al [ 41 ] investigated the effects of GPS on renal cell carcinoma (RCC) and its molecular mechanism for the first time. Studies concluded that the cell viability of 786-O and Caki-1 treated with gradient concentration of GPS (0, 75, 150, 300, 600 µg/mL) for 24 h showed a significant decrease.…”

Section: Pharmacological Properties Of Gpmentioning

confidence: 99%

Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum

Ren

et al. 2021

Molecules

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Gynostemma pentaphyllum (Thunb.) Makino (GP), also named Jiaogulan in Chinese, was known to people for its function in both health care and disease treatment. Initially and traditionally, GP was a kind of tea consumed by people for its pleasant taste and weight loss efficacy. With the passing of the centuries, GP became well known as more than just a tea. Until now, numbers of bioactive compounds, including saponins (also named gypenosides, GPS), polysaccharides (GPP), flavonoids, and phytosterols were isolated and identified in GP, which implied the great medicinal worth of this unusual tea. Both in vivo and in vitro tests, ranging from different cell lines to animals, indicated that GP possessed various biological activities including anti-cancer, anti-atherogenic, anti-dementia, and anti-Parkinson’s diseases, and it also had lipid-regulating effects as well as neuroprotection, hepatoprotective, and hypoglycemic properties. With the further development and utilization of GP, the research on the chemical constituents and pharmacological properties of GP were deepening day by day and had made great progress. In this review, the recent research progress in the bioactive compounds, especially gypenosides, and the pharmacological activities of GP were summarized, which will be quite useful for practical applications of GP in the treatment of human diseases.

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Section: Pharmacological Properties Of Gpmentioning

confidence: 99%

Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum

Ren

et al. 2021

Molecules

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“…It is known that Gyp L, Gyp LI, and gypenosides can inhibit the proliferation of ccRCC cells in vitro ( Liu et al, 2021 ). We further confirmed whether gypenosides could inhibit tumor growth in vivo .…”

Section: Resultsmentioning

confidence: 99%

“…Notably, ERK1/2 regulates PKC protein in a dependent and independent manner, and further mediates cPLA2 phosphorylation and AA release in astrocytes ( Xu et al, 2002 ). We have demonstrated the efficacy of gypenosides in inducing apoptosis of renal cell carcinoma via activation of the PI3K/AKT/mTOR pathway ( Liu et al, 2021 ). This fits with previous research, which has shown that gypenosides inhibit the proliferation of liver and esophageal cancer by regulating the MAPK pathway ( Ma et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Gypenoside L and Gypenoside LI Inhibit Proliferation in Renal Cell Carcinoma via Regulation of the MAPK and Arachidonic Acid Metabolism Pathways

Liu

Xie

et al. 2022

Front. Pharmacol.

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Renal cell carcinoma (RCC) has the highest mortality rate of all urological malignancies. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of all RCC cases and is often accompanied by the accumulation of lipid droplets. Growing evidence indicates that ccRCC is a metabolism-related disease. Gypenosides are commonly used for the clinical treatment of hyperlipidemia, and their antitumor activity has also been recognized. However, the potential inhibitory effects and mechanisms of action of gypenoside L (Gyp L) and gypenoside LI (Gyp LI) in ccRCC remain unclear. In this study, we confirmed that Gyp L and Gyp LI significantly inhibited proliferation and induced apoptosis in ccRCC cells in vitro. We performed network pharmacology and RNA-seq, and verified the results by Western blotting, RT-qPCR, and immunofluorescence experiments. Our results demonstrated that Gyp L and Gyp LI upregulate the expression of COX2 and downregulate the expression levels of cPLA2 and CYP1A1, resulting in reduced arachidonic acid and apoptosis. Gyp L and Gyp LI upregulated the protein levels of DUSP1, p-JUN, and p-JNK, and downregulated p-MEK1/2, p-ERK, and p-P38 levels. Moreover, gypenosides significantly inhibited tumor growth in vivo, and gypenosides significantly reduced cPLA2 and CYP1A1 expression. Furthermore, we performed absolute quantification of arachidonic acid (AA) content in ccRCC cells and tumor tissues by HPLC-MS, and found that the arachidonic acid content was significantly reduced after Gyp L, Gyp LI, and gypenoside intervention. In conclusion, our data suggest that Gyp L, Gyp LI, and gypenosides decrease the content of arachidonic acid in ccRCC cells and tumor tissues, but do not have cytotoxic effects on nude mice. Thus, Gyp L, Gyp LI, and total gypenosides extracted from Gynostemma pentaphyllum exhibited antitumor activities against ccRCC.

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“…BATF belongs to the AP-1/ATF superfamily and taken as a negative regulator in the events of AP-1/ATF transcription [7]. According to Gene Ontology annotations, BATF referred to DNA-binding transcription factor activity and sequence-speci c DNA binding [8]. As we know, AP-1 family transcription factor plays an important role in the differentiation of lineage-speci c cells in the immune system.…”

Section: Discussionmentioning

confidence: 99%

BATF Inhibits Cell Proliferation and Migration via PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma

Li¹,

Jin²,

Yang³

et al. 2021

Preprint

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Background Previous studies reported that BATF played an important role in the progression of various cancers, but no report had been found on clear cell renal cell carcinoma(ccRCC). So we investigated the effects of BATF on the progression of ccRCC. Methods In this study, using TCGA-KIRC database from the Cancer Genome Atlas to analyze the differential genes of BATF in ccRCC ; using immunohistochemistry to detect BATF expression in 75 ccRCC tumorous and 28 nontumorous tissues, and investigate its relationship with clinicopathological parameters. Moreover, we constructed the cell lines of BATF overexpression and knockout in Caki-1and 786-0 ccRCC cell lines and confirmed by western blot. CCK8 assay was used to evaluated the cell viability and using EdU staining to detect cell proliferation; using Transwell experiment to investigate the affection of BATF in ccRCC cell migration. Westernblot was used to detect the phosphorylation of PI3K/AKT/mTOR. Results These results revealed that BATF expression in ccRCC tumorous was significantly higher compared with that in adjacent nontumorous tissues and was significantly correlated with T stage, Fuhrman grade, Tumor necrosis and status. In addiditon, BATF overexpression significantly inhibited the viability, proliferation and migration of the two cell lines. More importantly, using westernblot showed that silencing BATF significantly increased the level of phosphorylated AKT, PI3K and mTOR, while BATF overexpression decreased phosphorylation that involved in the PI3K/Akt/mTOR signaling pathway. Conclusions Our findings demonstrate that BATF plays an important role in the progression of ccRCC and it may act as an tumor supressor gene to inhibit the progression of ccRCC through regulating the PI3K/Akt/mTOR signaling pathway.

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Mechanism of gypenosides of Gynostemma pentaphyllum inducing apoptosis of renal cell carcinoma by PI3K/AKT/mTOR pathway

Cited by 46 publications

References 31 publications

Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum

Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum

Gypenoside L and Gypenoside LI Inhibit Proliferation in Renal Cell Carcinoma via Regulation of the MAPK and Arachidonic Acid Metabolism Pathways

BATF Inhibits Cell Proliferation and Migration via PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma

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