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Planta Med. 2019 Mar;85(5):394-405. doi: 10.1055/a-0810-7738. Epub 2018 Dec 18.

Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells.

Xing SF1,2, Liu LH3, Zu ML1,2, Lin M1,2, Zhai XF1,2, Piao XL1,2.

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School of Pharmacy, Minzu University of China, Beijing, China.
Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China.
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Liaoning, Dalian, China.


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.

[Indexed for MEDLINE]

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