Histone Methyltransferase Setd7 Regulates Nrf2 Signaling Pathway by Phenethyl Isothiocyanate and Ursolic Acid in Human Prostate Cancer Cells

被引：41
作者：
Wang, Chao [1 ,2 ]
Shu, Limin [1 ,2 ]
Zhang, Chengyue [1 ,2 ]
Li, Wenji [1 ,2 ]
Wu, Renyi [1 ,2 ]
Guo, Yue [1 ,2 ]
Yang, Yuqing [1 ,2 ]
Kong, Ah-Ng [1 ,2 ]
机构：
[1] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, Piscataway, NJ 08854 USA
[2] Rutgers State Univ, Ernest Mario Sch Pharm, Ctr Phytochem Epigenome Studies, Piscataway, NJ 08854 USA
来源：
MOLECULAR NUTRITION & FOOD RESEARCH | 2018年 / 62卷 / 18期
关键词：
Nrf2; oxidative stress; PEITC; prostate cancer cells; Setd7; LYSINE METHYLATION; INDUCED APOPTOSIS; IN-VIVO; ANTIOXIDANT RESPONSE; ACTIVATING NRF2; DNA-DAMAGE; SET7/9; TRANSCRIPTION; ACETYLATION; VEGETABLES;
D O I：
10.1002/mnfr.201700840
中图分类号：
TS2 [食品工业];
学科分类号：
0832 ;
摘要：
ScopeThis study aims to investigate the role of the epigenetic regulator SET domain-containing lysine methyltransferase 7 (Setd7) in regulating the antioxidant Nrf2 pathway in prostate cancer (PCa) cells and examines the effects of two phytochemicals, phenethyl isothiocyanate (PEITC) and ursolic acid (UA). Methods and resultsLentivirus-mediated shRNA knockdown of Setd7 in LNCaP and PC-3 cells decreases the expression of downstream Nrf2 targets, such as NAD(P)H: quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase theta 2 (Gstt2). Downregulation of Setd7 decreases soft agar colony formation ability of PCa cells. Knockdown of Setd7 increases reactive oxygen species (ROS) generation. Furthermore, Setd7 knockdown attenuates Nqo1 and Gstt2 expression in response to H2O2 challenge, whereas increased DNA damage is observed in Setd7 knockdown cells in comet assay. Interestingly, Setd7 expression could be induced by the dietary phytochemicals PEITC and UA. Chromatin immunoprecipitation (ChIP) assays show that Setd7 knockdown decreased H3K4me1 enrichment in the Nrf2 and Gstt2 promoter regions, while PEITC and UA treatments elevated the enrichment. ConclusionTaken together, these results indicate that Setd7 knockdown decreases Nrf2 and Nrf2-target genes expression and that PEITC and UA induce Setd7 expression, which activates the Nrf2/antioxidant response element (ARE) signaling pathway and protects DNA from oxidative damage.
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页数：11
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