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学科主题: 药学
题名:
Epigenetic Modifications of Nrf2 by 3,3 ′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
作者: Wu, Tien-Yuan1; Khor, Tin Oo1; Su, Zheng-Yuan1; Saw, Constance Lay-Lay1; Shu, Limin1; Cheung, Ka-Lung1; Huang, Ying1; Yu, Siwang2; Kong, Ah-Ng Tony1
关键词: 3,3 &prime ; -diindolylmethane (DIM) ; epigenetic ; methylation ; Nrf2 ; prostate cancer
刊名: AAPS JOURNAL
发表日期: 2013-07-01
DOI: 10.1208/s12248-013-9493-3
卷: 15, 期:3, 页:864-874
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: DNA METHYLATION ; CANCER-CELLS ; TRANSGENIC ADENOCARCINOMA ; OXIDATIVE STRESS ; MICE ; INDOLE-3-CARBINOL ; EXPRESSION ; MOUSE ; PHARMACODYNAMICS ; CHEMOPREVENTION
英文摘要:

3,3′-diindolylmethane (DIM) is currently being investigated in many clinical trials including prostate, breast, and cervical cancers and has been shown to possess anticancer effects in several in vivo and in vitro models. Previously, DIM has been reported to possess cancer chemopreventive effects in prostate carcinogenesis in TRAMP mice; however, the in vivo mechanism is unclear. The present study aims to investigate the in vitro and in vivo epigenetics modulation of DIM in TRAMP-C1 cells and in TRAMP mouse model. In vitro study utilizing TRAMP-C1 cells showed that DIM suppressed DNMT expression and reversed CpG methylation status of Nrf2 resulting in enhanced expression of Nrf2 and Nrf2-target gene NQO1. In vivo study, TRAMP mice fed with DIM-supplemented diet showed much lower incidence of tumorigenesis and metastasis than the untreated control group similar to what was reported previously. DIM increased apoptosis, decreased cell proliferation and enhanced Nrf2 and Nrf2-target gene NQO1 expression in prostate tissues. Importantly, immunohistochemical analysis showed that DIM reduced the global CpG 5-methylcytosine methylation. Focusing on one of the early cancer chemopreventive target gene Nrf2, bisulfite genomic sequencing showed that DIM decreased the methylation status of the first five CpGs of the Nrf2 promoter region, corroborating with the results of in vitro TRAMP-C1 cells. In summary, our current study shows that DIM is a potent cancer chemopreventive agent for prostate cancer and epigenetic modifications of the CpG including Nrf2 could be a potential mechanism by which DIM exerts its chemopreventive effects.

语种: 英语
WOS记录号: WOS:000321041000024
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66603
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Rutgers State Univ, Dept Pharmaceut, Ctr Canc Prevent Res, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA
2.Peking Univ, Hlth Sci Ctr, Dept Biol Chem, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wu, Tien-Yuan,Khor, Tin Oo,Su, Zheng-Yuan,et al. Epigenetic Modifications of Nrf2 by 3,3 ′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors[J]. AAPS JOURNAL,2013,15(3):864-874.
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