KMID : 1034820180140040417
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Molecular & Cellular Toxicology 2018 Volume.14 No. 4 p.417 ~ p.424
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MAC inhibits c-Myc and induces autophagy by downregulation of CIP2A in leukemia cells
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Hwang Soon-Kyung
Jeong Yun-Jeong Shin Jae-Moon Magae Junji Kim Cheorl-Ho Chang Young-Chae
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Abstract
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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.
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KEYWORD
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Autophagy, c-Myc, CIP2A, 4-O-methyl-ascochlorin (MAC), Leukemia cell
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