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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.

Author information

1
School of Pharmacy, Minzu University of China, Beijing, China.
2
Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China.
3
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Liaoning, Dalian, China.

Abstract

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.

PMID:
30562828
DOI:
10.1055/a-0810-7738
[Indexed for MEDLINE]

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