Home
Resources
Publications
WY-14643 Regulates CYP1B1 Expression Through Peroxisome Proliferator-Activated Receptor α-Mediated Signaling in Human Breast Cancer Cells

WY-14643 Regulates CYP1B1 Expression Through Peroxisome Proliferator-Activated Receptor α-Mediated Signaling in Human Breast Cancer Cells

Yong Pil Hwang, Seong Su Won, Sun Woo Jin, Gi Ho Lee, Thi Hoa Pham, Jae Ho Choi, Keon Wook Kang, Hye Gwang Jeong

Int J Mol Sci. 2019 Nov 25;20(23):5928.

PMID: 31775380

Abstract:

Human cytochrome P450 1B1 (CYP1B1)-mediated biotransformation of endobiotics and xenobiotics plays an important role in the progression of human breast cancer. In this study, we investigated the effects of WY-14643, a peroxisome proliferator-activated receptor α (PPARα) agonist, on CYP1B1 expression and the related mechanism in MCF7 breast cancer cells. We performed quantitative reverse transcription-polymerase chain reaction, transient transfection, and chromatin immunoprecipitation to evaluate the effects of PPARα on peroxisome proliferator response element (PPRE)-mediated transcription. WY-14643 increased the protein and mRNA levels of CYP1B1, as well as promoter activity, in MCF-7 cells. Moreover, WY-14643 plus GW6471, a PPARα antagonist, significantly inhibited the WY-14643-mediated increase in CYP1B1 expression. PPARα knockdown by a small interfering RNA markedly suppressed the induction of CYP1B1 expression by WY-14643, suggesting that WY-14643 induces CYP1B1 expression via a PPARα-dependent mechanism. Bioinformatics analysis identified putative PPREs (-833/-813) within the promoter region of the CYP1B1 gene. Inactivation of these putative PPREs by deletion mutagenesis suppressed the WY-14643-mediated induction of CYP1B1 promoter activation. Furthermore, WY-14643 induced PPARα to assume a form capable of binding specifically to the PPRE-binding site in the CYP1B1 promoter. Our findings suggest that WY-14643 induces the expression of CYP1B1 through activation of PPARα.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP50892234	WY-14643		50892-23-4	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: