MAC inhibits c-Myc and induces autophagy by downregulation of CIP2A in leukemia cells

Abstract

Backgrounds: 4-O-methyl-ascochlorin (MAC) is a methylated derivative of the prenyl-phenol antibiotic ascochlorin, which was isolated from the incomplete fungus Ascochyta viciae. We have recently shown that MAC promotes apoptotic cell death by inhibiting c-Myc expression in K562 leukemia cells, but the effects of MAC on autophagy are still unknown. Methods: Treatment of MAC significantly increased LC3 expression and autophagic vesicle formation by western blot and acridine orange staining. Also, we examined the possible mechanisms underlying MAC induced autophagy. Results: We found that MAC suppressed c-Myc expression by inhibiting CIP2A (regulator of c-Myc) protein synthesis. This result suggests that the downregulation of c-Myc expression plays the role of inducing apoptosis and autophagy by MAC treatment in human leukemia cells. Conclusion: These findings significantly contributed to the understanding of the mechanism that accounts for the anticancer activity of MAC, and it may be novel anti-cancer therapeutic agents for leukemia cells. © 2018, The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Nature B.V.