Browse > Article
http://dx.doi.org/10.7314/APJCP.2013.14.10.5663

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

Tamgue, Ousman (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Chai, Cheng-Sen (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Hao, Lin (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Zambe, John-Clotaire Daguia (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Huang, Wei-Wei (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Zhang, Bin (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Lei, Ming (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Wei, Yan-Ming (Key Laboratory of Agricultural Molecular Biology, College of Life Science, Northwest A&F University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.10, 2013 , pp. 5663-5669 More about this Journal
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.
Keywords
EZH2; EZH2 target genes; prostate cancer (PCa); Triptolide;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Zhao F, Chen Y, Li R, et al (2010). Triptolide alters histone H3K9 and H3K27 methylation state and induces G0/G1 arrest and caspase-dependent apoptosis in multiple myeloma in vitro. Toxicology, 267, 70-9.   DOI   ScienceOn
2 Zhu W, Ou Y, Li Y, et al (2009). A small-molecule triptolide suppresses angiogenesis and invasion of human anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor-kappa B pathway. Mol Pharmacol, 75, 812-9.   DOI   ScienceOn
3 Crea F, Hurt EM, Mathews LA, et al (2011). Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. Mol Cancer, 10, 40.   DOI   ScienceOn
4 Cao Q, Yu J, Dhanasekaran SM, et al (2008). Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene, 27, 7274-84.   DOI   ScienceOn
5 Chang CJ, Hung MC (2012). The role of EZH2 in tumour progression. Br J Cancer, 106, 243-7.   DOI   ScienceOn
6 Chase A, Cross NC (2011). Aberrations of EZH2 in Cancer. Clin Cancer Res, 17, 2613-8.   DOI   ScienceOn
7 Ellis L, Atadja PW, Johnstone RW (2009). Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther, 8, 1409-20.
8 Etchegaray JP, Yang X, DeBruyne JP, et al (2006). The polycomb group protein EZH2 is required for mammalian circadian clock function. J Biol Chem, 281, 21209-15.   DOI   ScienceOn
9 Feldman BJ, Feldman D (2001). The development of androgen-independent prostate cancer. Nat Rev Cancer, 1, 34-45.   DOI   ScienceOn
10 Fussbroich B, Wagener N, Macher-Goeppinger S, et al (2011). EZH2 depletion blocks the proliferation of colon cancer cells. PLoS One, 6, e21651.   DOI
11 Gil J, Bernard D, Peters G (2005). Role of polycomb group proteins in stem cell self-renewal and cancer. DNA Cell Biol, 24, 117-25.   DOI   ScienceOn
12 Kiviharju TM, Lecane PS, Sellers RG, et al (2002). Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin Cancer Res, 8, 2666-74.
13 Huang W, He T, Chai C, et al (2012). Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression. PLoS One, 7, e37693.   DOI
14 Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.   DOI
15 Kamminga LM, Bystrykh LV, de Boer A, et al (2006). The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood, 107, 2170-9.   DOI   ScienceOn
16 Liu J, Jiang Z, Xiao J, et al (2009). Effects of triptolide from Tripterygium wilfordii on ERalpha and p53 expression in two human breast cancer cell lines. Phytomedicine, 16, 1006-13.   DOI   ScienceOn
17 Min J, Zaslavsky A, Fedele G, et al (2010). An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med, 16, 286-94.   DOI   ScienceOn
18 Phillips PA, Dudeja V, McCarroll JA, et al (2007). Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res, 67, 9407-16.   DOI   ScienceOn
19 Plath K, Fang J, Mlynarczyk-Evans SK, et al (2003). Role of histone H3 lysine 27 methylation in X inactivation. Science, 300, 131-5.   DOI   ScienceOn
20 Ren SC, Chen R, Sun YH (2013). Prostate cancer research in China. Asian J Androl, 15, 350-3.   DOI   ScienceOn
21 Shi B, Liang J, Yang X, et al (2007). Integration of estrogen and Wnt signaling circuits by the polycomb group protein EZH2 in breast cancer cells. Mol Cell Biol, 27, 5105-19.   DOI   ScienceOn
22 Saramaki OR, Tammela TL, Martikainen PM, et al (2006). The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer. Genes Chromosomes Cancer, 45, 639-45.   DOI   ScienceOn
23 Sauvageau M, Sauvageau G (2010). Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell, 7, 299-313.   DOI   ScienceOn
24 Schulz WA, Hatina J (2006). Epigenetics of prostate cancer: beyond DNA methylation. J Cell Mol Med, 10, 100-25.   DOI
25 Su IH, Basavaraj A, Krutchinsky AN, et al (2003). Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol, 4, 124-31.   DOI   ScienceOn
26 Su IH, Dobenecker MW, Dickinson E, et al (2005). Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell, 121, 425-36.   DOI   ScienceOn
27 Titov DV, Gilman B, He QL, et al (2011). XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat Chem Biol, 7, 182-8.   DOI   ScienceOn
28 Wang Y, Lu JJ, He L, et al (2011). Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II). PLoS One, 6, e23993.   DOI
29 Wang Z, Jin H, Xu R, et al (2009). Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression. Exp Mol Med, 41, 717-27.   DOI   ScienceOn
30 Yu J, Yu J, Mani RS, et al (2010). An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer Cell, 17, 443-54.   DOI   ScienceOn
31 Westerheide SD, Kawahara TL, Orton K, et al (2006). Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J Biol Chem, 281, 9616-22.   DOI   ScienceOn
32 Wu SC, Zhang Y (2011). Cyclin-dependent kinase 1 (CDK1)-mediated phosphorylation of enhancer of zeste 2 (Ezh2) regulates its stability. J Biol Chem, 286, 28511-9.   DOI   ScienceOn
33 Yu J, Cao Q, Mehra R, et al (2007). Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell, 12, 419-31.   DOI   ScienceOn
34 Zhao F, Chen Y, Zeng L, et al (2010). Role of triptolide in cell proliferation, cell cycle arrest, apoptosis and histone methylation in multiple myeloma U266 cells. Eur J Pharmacol, 646, 1-11.   DOI   ScienceOn
35 Antonoff MB, Chugh R, Borja-Cacho D, et al (2009). Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo. Surgery, 146, 282-90.   DOI   ScienceOn
36 O'Carroll D, Erhardt S, Pagani M, et al (2001). The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol, 21, 4330-6.   DOI   ScienceOn
37 Varambally S, Dhanasekaran SM, Zhou M, et al (2002). The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature, 419, 624-9.   DOI   ScienceOn