β-Elemene induces apoptosis and autophagy in colorectal cancer cells through regulating the ROS/AMPK/mTOR pathway.

Abstract

β-Elemene is an effective anti-cancer ingredient extracted from the genus Curcuma (Zingiberaceae familiy). In the present study, we demonstrated that β-elemene inhibited the proliferation of colorectal cancer cells and induced cell cycle arrest in the G2/M phase. In addition, β-elemene induced nuclear chromatin condensation and cell membrane phosphatidylserine eversion, decreased cell mitochondrial membrane potential, and promoted the cleavage of caspase-3, caspase-9 and PARP proteins, indicating apoptosis in colorectal cancer cells. At the same time, β-elemene induced autophagy response, and the treated cells showed autophagic vesicle bilayer membrane structure, which was accompanied by up-regulation of the expression of LC3B and SQSTM1. Furthermore, β-elemene increased ROS levels in colorectal cancer cells, promoted phosphorylation of AMPK protein, and inhibited mTOR protein phosphorylation. In the experiments in vivo, β-elemene inhibited the tumor size and induced apoptosis and autophagy in nude mice. In summary, β-elemene inhibited the occurrence and development of colon cancer xenografts in nude mice, and significantly induced apoptosis and autophagy in colorectal cancer cells in vitro. These effects were associated with regulation of the ROS/AMPK/mTOR signaling. We offered a molecular basis for the development of β-elemene as a promising anti-tumor drug candidate for colorectal cancer.

• Authors: Guo-Yu Wang, Lei Zhang, Ya-Di Geng, Bin Wang, Xiao-Jun Feng, Zhao-Lin Chen, Wei Wei, Ling Jiang
• Journal: Chinese journal of natural medicines (Chin J Nat Med) Vol. 20 Issue 1 Pg. 9-21 (Jan 2022) ISSN: 1875-5364 [Electronic] China
• PMID: 35101253 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Sesquiterpenes
• beta-elemene
• MTOR protein, human
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics)
• Animals
• Apoptosis
• Autophagy
• Cell Line, Tumor
• Colorectal Neoplasms (drug therapy, genetics)
• Humans
• Mice
• Mice, Nude
• Reactive Oxygen Species
• Sesquiterpenes
• TOR Serine-Threonine Kinases (genetics)