title: Triptolide inhibits histone methyltransferase EZH2 and modulates the expression of its target genes in prostate cancer cells.
abstract: The histone methyltransferase EZH2 (enhancer of zeste homolog 2) plays critical roles in prostate cancer (PCa) development and is a potential target for PCa treatment. Triptolide possesses anti-tumor activity, but it is unknown whether its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a target for Triptolide in PCa cells. Our data showed that Triptolide suppressed PCa cell growth and reduced the expression of EZH2. Overexpression of EZH2 attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolide treatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2, CDH1, CDKN2A and DAB2IP) negatively regulated by EZH2 as well as reduced mRNA levelsan of EZH2 positively regulated gene (cyclin D1). Our findings suggest the PCa cell growth inhibition mediated by Triptolide might be associated with downregulation of EZH2 expression and the subsequent modulation of target genes.
authors.affiliation: Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A and F University, Yangling, China E-mail : leiming70@hotmail.com, weiyanming2005@aliyun.com.
authors.forename: Ousman
authors.initials: O
authors.lastname: Tamgue
authors.forename: Cheng-Sen
authors.initials: CS
authors.lastname: Chai
authors.forename: Lin
authors.initials: L
authors.lastname: Hao
authors.forename: John-Clotaire Daguia
authors.initials: JC
authors.lastname: Zambe
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Wei
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D004852:Epoxy Compounds / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D010616:Phenanthrenes / Q000494:pharmacology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D012333:RNA, Messenger; C001899:triptolide; D000076983:Histone Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2