A steroidal saponin isolated from Allium chinense simultaneously induces apoptosis and autophagy by modulating the PI3K/Akt/mTOR signaling pathway in human gastric adenocarcinoma.

作者: Jingwen Xu , Mingmei Zhang , Xiaoying Lin , Yihai Wang , Xiangjiu He

DOI: 10.1016/J.STEROIDS.2020.108672

关键词:

摘要: Abstract Allium chinense, as a side dish on Asian table, is often used in folk medicine for its health benefits. (25R)-5α-spirostan-3β-yl-3-O-acetyl-O-β- d -glucopyranosyl-(1 → 2)-O-[β- -glucopyranosyl-(1 → 3)]-O-β- -glucopyranosyl-(1 → 4)-β- -galactopyranoside (A-24) bioactive steroidal saponin isolated from chinense. Previously, we have shown that A-24 has cytotoxic effects cancer cells, but not normal cells. To further explore the underlying mechanisms, this study, investigated anticancer activity of human gastric cell lines terms proliferation, colony formation, cycle, induction apoptosis/autophagy, and PI3K/Akt/mTOR pathway. showed dose-dependent cytotoxicity SGC-7901 AGS lines, it induced intrinsic mitochondrial pathway apoptosis well autophagy, G2/M phase arrest modulation cyclinB1, p-cdc2, p-wee1 p-Histone H3 expression. Furthermore, downregulated phosphorylation Akt at Ser473 mTOR Ser2448 pathway, downstream substrates p-p70S6K p-4EBP1 manner. In addition, pre-treatment tumor cells with 3-methyladenine (3-MA) LY294002 increased A-24-induced apoptosis. Collectively, these findings highlight significance downregulation potential application novel candidate treatment adenocarcinoma.

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