β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

BMC Cancer. 2011 May 20;11:183. doi: 10.1186/1471-2407-11-183.

Abstract

Background: β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved.

Results: β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene.

Conclusions: Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Stomach Neoplasms / physiopathology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts
  • Sesquiterpenes
  • beta-elemene
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt