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

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

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.

MeSH terms

  • A549 Cells
  • Cell Cycle / drug effects
  • G1 Phase
  • Gynostemma / chemistry*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Signal Transduction
  • Structure-Activity Relationship
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Reactive Oxygen Species
  • Saponins
  • Triterpenes
  • dammarane