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Published on: June 30, 2023
β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis
Jing Liu1, Ye Zhang, Jinglei Qu
1Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, PR China.
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.
Insights
Beta-elemene, a natural compound, shows anti-cancer effects by inducing autophagy and apoptosis in gastric cancer cells. Combining beta-elemene with autophagy inhibitors may improve treatment for advanced gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Beta-elemene, derived from traditional Chinese medicine, exhibits broad-spectrum anti-cancer properties.
- The precise mechanism of beta-elemene's cytotoxic effects on cancer cells is not fully understood.
- Gastric cancer remains a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-tumor effects of beta-elemene on human gastric cancer cell lines.
- To elucidate the molecular mechanisms underlying beta-elemene's anti-cancer activity, focusing on apoptosis and autophagy.
- To explore the potential of combining beta-elemene with autophagy inhibitors for enhanced therapeutic efficacy.
Main Methods:
- Cell viability assays were performed on MGC803 and SGC7901 gastric cancer cells treated with varying concentrations of beta-elemene.
- Apoptosis was assessed through standard assays, and autophagy was evaluated by monitoring LC3 puncta, cellular morphology, and LC3-II protein levels.
- Western blotting was used to analyze the expression of autophagy-related proteins, including the Atg5-Atg12 conjugate, and to assess the activity of the PI3K/Akt/mTOR/p70S6K1 signaling pathway.
- Gene silencing of Beclin 1 and treatment with autophagy inhibitors (3-methyladenine, chloroquine) were employed to investigate the role of autophagy in beta-elemene's anti-tumor effects.
Main Results:
- Beta-elemene significantly inhibited the viability of human gastric cancer cells in a dose-dependent manner, primarily through the induction of apoptosis.
- Treatment with beta-elemene robustly induced autophagy, evidenced by increased LC3 dots and LC3-II protein levels, and upregulated the Atg5-Atg12 conjugate.
- Beta-elemene suppressed the PI3K/Akt/mTOR/p70S6K1 signaling pathway, and inhibiting autophagy (via Beclin 1 knockdown or chemical inhibitors) potentiated beta-elemene's anti-cancer effects.
Conclusions:
- Beta-elemene induces protective autophagy, which paradoxically prevents gastric cancer cells from undergoing apoptosis.
- The findings suggest that targeting autophagy in conjunction with beta-elemene administration could be a promising therapeutic strategy for advanced gastric cancer.
- This study provides novel insights into the complex interplay between beta-elemene, autophagy, and apoptosis in gastric cancer treatment.
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