Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy.

Abstract

Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. Furthermore, sesamol treatment elicited mitochondrial dysfunction by inducing a loss of mitochondrial membrane potential. Impaired mitochondria and accumulated H2O2 production resulted in disturbance of redox-sensitive signaling including Akt and MAPKs pathways. Mitochondrial biogenesis was inhibited as suggested by the decline in expression of mitochondrial complex I subunit ND1, and the upstream AMPK/PGC1α signals. Importantly, sesamol inhibited mitophagy and autophagy through impeding the PI3K Class III/Belin-1 pathway. Autophagy stimulator rapamycin reversed sesamol-induced apoptosis and mitochondrial respiration disorders. Moreover, it was also shown that sesamol has potent anti-hepatoma activity in a xenograft nude mice model. These data suggest that mitochondria play an essential role in sesamol-induced HepG2 cells death, and further research targeting mitochondria will provide more chemotherapeutic opportunities.

• Authors: Zhigang Liu, Bo Ren, Yihui Wang, Chen Zou, Qinglian Qiao, Zhijun Diao, Yashi Mi, Di Zhu, Xuebo Liu
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 45728 (04 04 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28374807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Benzodioxoles
• Phenols
• sesamol
• Sirolimus

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Benzodioxoles (pharmacology)
• Carcinoma, Hepatocellular (metabolism)
• Cell Proliferation (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (metabolism)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice, Nude
• Mitochondria (drug effects, metabolism)
• Phenols (pharmacology)
• Sirolimus (pharmacology)
• Xenograft Model Antitumor Assays