Heat-processed Gynostemma pentaphyllum has shown strong activity against human lung carcinoma A549 cells. In this study, two new dammarane-type saponins together with two known compounds were isolated from the ethanol extract of the heat-processed leaves of G. pentaphyllum. They were identified as 2α,3β,12β-trihydroxydammar-20(22),24-diene-3-O-β-D-glucopyranoside (1, namely damulin E), 2α,3β,12β-trihydroxydammar-20(21),24-diene-3-O-β-D-glucopyranoside (2, namely damulin F), damulin A (3) and damulin B (4), respectively, using IR, NMR and mass spectra.Damulin E and damulin F showed strong anti-cancer activity against A549, H1299, T24, SH-SY5Y and K562 cell lines in vitro using CCK-8 assay.

Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.

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