Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells

Clinical Epigenetics

Emily Ho¹  Roderick H Dashwood²  David E Williams²  Zhen Yu²  Carmen P Wong¹  Anna Hsu¹ 

[1] Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331, USA;Department of Environmental & Molecular Toxicology, 1007 Ag Life Sciences Building, Oregon State University, Corvallis, OR 97331, USA

关键词: chemo-prevention;    cyclins;    prostate cancer;    methylation;    Sulforaphane;   

Others  :  791546
DOI  :  10.1186/1868-7083-3-3

 received in 2011-04-19, accepted in 2011-10-26,  发布年份 2011

【 摘 要 】

Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC) enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.

【 授权许可】

   
2011 Hsu et al; licensee BioMed Central Ltd.

【 图 表 】

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