In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5374-5374
Abstract:
Prostate cancer is one of the most deadly malignancies among men in the United States. Recent evidence suggests epigenetic alteration is involved during the development and progression of prostate cancer. Previously we have demonstrated that Nrf2, a key regulator of cellular antioxidant defense systems, was epigenetically silenced in TRAMP prostate cancers, as well as tumorigenic TRAMP C1 cells. Sulforaphane (SFN), an isothiocyanate rich in cruciferous vegetables, has been shown to be a potent cancer prevention agent for years. The aim of this study is to investigate the potential of SFN to reactivate the expression of Nrf2 in TRAMP C1 cells via epigenetic modifications. Bisulfite genomic sequencing (BGS) showed that treatment of SFN resulted in demethylation of the first 5 CpGs in the promoter region of Nrf2 gene. Methylation DNA immunoprecipitation (MeDIP) analysis revealed that SFN significantly reduced the anti-mecyt antibody binding to the first 5 CpGs of the Nrf2 promoter, corresponding to the BGS results. Reversion of the methylation status was found to be associated with re-expression of Nrf2 and its downstream NQO-1 at the mRNA and protein levels. Further analysis showed that SFN treatment decreased the expression of DNA methyltransferases (DNMTs), particularly DNMT1 and DNMT3a. Though SFN treatment showed differential effects on the protein expression of various HDACs, it increased the global level of active chromatin marker acetyl-H3. Taken together, our study suggests that SFN may exert its chemoprevention effect through epigenetic regulation modification of Nrf2 gene with subsequent induction of its downstream anti-oxidative stress pathway. Citation Format: Chengyue Zhang, Zheng-Yuan Su, Tin Oo Khor, Ah-Ng Kong. Sulforaphane reactivates the expression of Nrf2 through CpGs demethylation in TRAMP C1 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5374. doi:10.1158/1538-7445.AM2013-5374
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-5374
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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