title: c-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells.
abstract: 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.
authors.affiliation: a Department of Pharmacology & Chemical Biology , University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania , USA.|b University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania , USA.
authors.forename: Eun-Ryeong
authors.initials: ER
authors.lastname: Hahm
authors.affiliation: a Department of Pharmacology & Chemical Biology , University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania , USA.|b University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania , USA.
authors.forename: Krishna Beer
authors.initials: KB
authors.lastname: Singh
authors.affiliation: a Department of Pharmacology & Chemical Biology , University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania , USA.|b University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania , USA.
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011944:Receptors, Androgen; C410798:AR protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: EZH2; androgen receptor; c-Myc; chemoprevention; honokiol; prostate cancer