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Abstract Title:

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

Abstract Source:

Mol Nutr Food Res. 2018 Jan 30. Epub 2018 Jan 30. PMID: 29383876

Abstract Author(s):

Chao Wang, Limin Shu, Chengyue Zhang, Wenji Li, Renyi Wu, Yue Guo, Yuqing Yang, Ah-Ng Kong

Article Affiliation:

Chao Wang

Abstract:

SCOPE: This study aimed 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 examined the effects of two phytochemicals, phenethyl isothiocyanate (PEITC) and ursolic acid (UA).

METHODS AND RESULTS: Lentivirus-mediated shRNA knockdown of Setd7 in LNCaP and PC-3 cells decreased the expression of downstream Nrf2 targets, such as NAD(P)H: quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase theta 2 (Gstt2). Down-regulation of Setd7 decreased soft agar colony formation ability of PCa cells. Knockdown of Setd7 increased reactive oxygen species (ROS) generation. Furthermore, Setd7 knockdown attenuated Nqo1 and Gstt2 expression in response to HOchallenge, whereas increased DNA damage was 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 showed that Setd7 knockdown decreased H3K4me1 enrichment in the Nrf2 and Gstt2 promoter regions, while PEITC and UA treatments elevated the enrichment.

CONCLUSION: Taken 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. This article is protected by copyright. All rights reserved.

Study Type : In Vitro Study

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