Triptolide Inhibits Histone Methyltransferase EZH2 and Modulates the Expression of Its Target Genes in Prostate Cancer Cells

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 itis unknown whether its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a target forTriptolide in PCa cells. Our data showed that Triptolide suppressed PCa cell growth and reduced the expressionof EZH2. Overexpression of EZH2 attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolidetreatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2, CDH1, CDKN2A andDAB2IP) 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 withdownregulation of EZH2 expression and the subsequent modulation of target genes.