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  • Title: The inhibitory effect of gypenoside stereoisomers, gypenoside L and gypenoside LI, isolated from Gynostemma pentaphyllum on the growth of human lung cancer A549 cells.
    Author: Xing SF, Liu LH, Zu ML, Ding XF, Cui WY, Chang T, Piao XL.
    Journal: J Ethnopharmacol; 2018 Jun 12; 219():161-172. PubMed ID: 29545210.
    Abstract:
    ETHNOPHARMACOLOGICAL RELEVANCE: Gypenosides are major constituents in Gynostemma pentaphyllum (Thunb.) Makino. Previous studies have shown that gypenosides isolated from G. pentaphyllum possess inhibitory effect on the growth of cancer cells, especially A549 cells, with structure-activity relationship (SAR). However, the underlying mechanism of gypenoside-induced A549 cell death remains to be clarified. AIM OF THE STUDY: To further investigate SAR and the underlying mechanism of gypenosides in A549 cells. MATERIALS AND METHODS: Gypenosides were isolated from G. pentaphyllum using chromatography methods and identified using MS and NMR data. The cytotoxicity was determined with CCK-8 assay. The effects of gypenosides on apoptosis, cell cycle and migration were investigated through cell morphology observation, flow cytometry analysis and key proteins detection. RESULTS: Three gypenosides, 2α,3β,12β,20(S)-tetrahydroxydammar-24-ene-3-O-β-D-glucopyranoside-20-O-β-D-glucopyranoside, gypenoside L and gypenoside LI were isolated from G. pentaphyllum. Gypenoside stereoisomers, gypenoside L (S configuration at C20) and gypenoside LI (R configuration at C20) showed stronger activity against A549 cells. Furthermore, both induced A549 cell apoptosis through intrinsic and extrinsic pathways evidenced by reducing mitochondrial membrane potential (MMP), generating reactive oxygen species (ROS), releasing more cytochrome c and down-regulating procaspase 8. However, gypenoside L blocked A549 cells in G0/G1, while gypenoside LI induced G2/M arrest, which was further verified by different expression of CDK1, CDK2 and CDK4. In addition, both inhibited A549 cell migration, which was evidenced by down-regulation of MMP-2/9 as well as scratch wound assay and transwell assay. CONCLUSION: C20 of gypenoside played an important role in A549 cell cytotoxicity and gypenoside stereoisomers could be used as potential multi-target chemopreventive agents for cancer.
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