Cyclovirobuxine D Inhibits Cell Proliferation and Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer Cells

Molecules. 2015 Nov 19;20(11):20659-68. doi: 10.3390/molecules201119729.

Abstract

Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects of CVB-D on gastric cancer cells and the underlying mechanisms of action. CVB-D reduced cell viability and colony formation ability of MGC-803 and MKN28 cells in a time- and concentration-dependent manner. Flow cytometry showed that cell cycle of CVB-D treated cells was arrested at the S-phase. CVB-D also induced apoptosis in MGC-803 and MKN28 cells, especially early stage apoptosis. Furthermore, mitochondria membrane potential (Δψm) was reduced and apoptosis-related proteins, cleaved Caspase-3 and Bax/Bcl-2, were up-regulated in CVB-D-treated MGC-803 and MKN28 cells. Taken together, our studies found that CVB-D plays important roles in inhibition of gastric tumorigenesis via arresting cell cycle and inducing mitochondria-mediated apoptosis, suggesting the potential application of CVB-D in gastric cancer therapy.

Keywords: apoptosis; cell cycle; cyclovirobuxine D; gastric cancer; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Drugs, Chinese Herbal
  • cyclovirobuxine D