c-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells
c-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells
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DOI：
10.1080/15384101.2016.1201253
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发表时间：
2016-01-01
期刊：
影响因子：
4.3
通讯作者：
Singh, Shivendra V.
中科院分区：
文献类型：
--
作者：
Hahm, Eun-Ryeong;Singh, Krishna Beer;Singh, Shivendra V.
和厚朴酚(Honokiol，HNK)是一种从厚朴属植物中提取的极具应用前景的植物化学物质，具有抗前列腺癌的体内外活性，但其作用机制尚不完全清楚。本研究旨在探讨c-Myc在HNK抗癌作用中的作用。前列腺癌细胞暴露于血浆可达剂量的HNK后，c-Myc总蛋白和/或磷酸化c-Myc蛋白及其mRNA的表达水平显著降低。我们还观察到口服HNK对PC-3异种移植瘤c-Myc蛋白的抑制作用。C-Myc在PC-3和22Rv1细胞中的稳定过表达对HNK介导的生长抑制和G(0)-G(1)期细胞周期停滞具有显著的保护作用。HNK治疗可降低c-Myc下游靶基因Cyclin D1和EZH2的表达，c-Myc过表达可部分恢复上述作用。此外，EZH2基因稳定敲除的PC-3和DU145细胞对HNK的生长抑制作用相对更敏感。最后，雄激素受体的过表达取消了HNK介导的c-Myc及其靶点的下调，尤其是EZH2。本研究表明，c-Myc是HNK抑制前列腺癌生长的新靶点，在前列腺癌的早期和晚期经常过表达。
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 G(0)-G(1) 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.