Abstract
Backgroundβ-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.Resultsβ-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.ConclusionsOur 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.
Highlights
Gastric cancer is one of the top three leading causes of cancer death in China
To further confirm that apoptosis was induced by b-elemene, western blotting was performed to detect the cleavage of caspase 3 as well as poly(ADP-ribose) polymerase (PARP)
We found that b-elemene inhibited the viability of SGC7901 cells in a dose-dependent manner, and the IC50 values at 24, 48 and 72 h were 89.68 μg/mL, 75.88 μg/mL and 67.13 μg/mL, respectively (Figure 6A). b-Elemene inhibited mTOR activity and induced apoptosis and autophagy, which were evidenced by the cleavage of PARP and the conversion of LC3-I to LC3-II (Figure 6B)
Summary
Gastric cancer is one of the top three leading causes of cancer death in China. In China, b-elemene has been used to Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome [10]. Autophagy is a mechanism for the turnover of proteins and elimination of damaged organelles to maintain cell homeostasis [11]. It starts with the formation of double membrane vesicles (autophagosomes) which engulf organelles or long-lived proteins. Autophagy is an important and decisive factor in the balance between cell death and survival
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