beta-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis
beta-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 beta-elemene kills cells remains unclear.
The aim of the present study is to investigate the anti-tumor effect of beta-elemene on human gastric cancer cells and the molecular mechanism involved.
beta-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 beta-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 beta-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 beta-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 beta-elemene.
Our data provides the first evidence that beta-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis.
A combination of beta-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer.