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Planta Med 2019; 85(05): 394-405
DOI: 10.1055/a-0810-7738
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

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

Shao-Fang Xing   *
1   School of Pharmacy, Minzu University of China, Beijing, China
2   Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China
,
Lin-Hua Liu   *
3   Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Liaoning, Dalian, China
,
Ma-Li Zu
1   School of Pharmacy, Minzu University of China, Beijing, China
2   Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China
,
Man Lin
1   School of Pharmacy, Minzu University of China, Beijing, China
2   Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China
,
Xin-Fang Zhai
1   School of Pharmacy, Minzu University of China, Beijing, China
2   Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China
,
Xiang-Lan Piao
1   School of Pharmacy, Minzu University of China, Beijing, China
2   Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China
› Author Affiliations
Further Information

Publication History

received 02 June 2018
revised 16 November 2018

accepted 29 November 2018

Publication Date:
18 December 2018 (online)

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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.

Key words

Gynostemma pentaphyllum - Curcubitaceae - saponin - damulin B - cytotoxicity - lung cancer

* Authorship note: Shao-Fang Xing and Lin-Hua Liu contributed equally to this work.


 

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