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Epigenetic Modifications of Nrf2 by 3,3 ′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
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
2013-07-01
DOI10.1208/s12248-013-9493-3
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
引用统计
被引频次:34[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66603
专题北京大学药学院_化学生物学系
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
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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.
APA Wu, Tien-Yuan.,Khor, Tin Oo.,Su, Zheng-Yuan.,Saw, Constance Lay-Lay.,Shu, Limin.,...&Kong, Ah-Ng Tony.(2013).Epigenetic Modifications of Nrf2 by 3,3 ′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors.AAPS JOURNAL,15(3),864-874.
MLA Wu, Tien-Yuan,et al."Epigenetic Modifications of Nrf2 by 3,3 ′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors".AAPS JOURNAL 15.3(2013):864-874.
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