c-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells

Honokiol (HNK), a highly promising phytochemical derived from Magnolia officinalis plant, exhibits in vitro and in vivo anticancer activity against prostate cancer but the underlying mechanism is not fully clear. This study was undertaken to delineate the role of c-Myc in anticancer effects of HNK....

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Published in:Cell cycle (Georgetown, Tex.) Tex.), 2016-09, Vol.15 (17), p.2309-2320
Main Authors: Hahm, Eun-Ryeong, Singh, Krishna Beer, Singh, Shivendra V
Format: Article
Language:English
Subjects:
Biphenyl Compounds - chemistry
Biphenyl Compounds - pharmacology
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cell Proliferation - drug effects
Down-Regulation - drug effects
Gene Expression Regulation, Neoplastic - drug effects
Humans
Lignans - chemistry
Lignans - pharmacology
Male
Phosphorylation
Prostatic Neoplasms - pathology
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
Receptors, Androgen
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary:Honokiol (HNK), a highly promising phytochemical derived from Magnolia officinalis plant, exhibits in vitro and in vivo anticancer activity against prostate cancer but the underlying mechanism is not fully clear. This study was undertaken to delineate the role of c-Myc in anticancer effects of HNK. Exposure of prostate cancer cells to plasma achievable doses of HNK resulted in a marked decrease in levels of total and/or phosphorylated c-Myc protein as well as its mRNA expression. We also observed suppression of c-Myc protein in PC-3 xenografts upon oral HNK administration. Stable overexpression of c-Myc in PC-3 and 22Rv1 cells conferred significant protection against HNK-mediated growth inhibition and G0-G1 phase cell cycle arrest. HNK treatment decreased expression of c-Myc downstream targets including Cyclin D1 and Enhancer of Zeste Homolog 2 (EZH2), and these effects were partially restored upon c-Myc overexpression. In addition, PC-3 and DU145 cells with stable knockdown of EZH2 were relatively more sensitive to growth inhibition by HNK compared with control cells. Finally, androgen receptor overexpression abrogated HNK-mediated downregulation of c-Myc and its targets particularly EZH2. The present study indicates that c-Myc, which is often overexpressed in early and late stages of human prostate cancer, is a novel target of prostate cancer growth inhibition by HNK.
ISSN:1538-4101
1551-4005
DOI:10.1080/15384101.2016.1201253