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PPAR Research

PPAR Research

IF: 3.1
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Fenofibrate Exerts Antitumor Effects in Colon Cancer via Regulation of DNMT1 and CDKN2A

Published:16 April 2021 DOI: 10.1155/2021/6663782 PMID: 33959155
Rui Kong, Nan Wang, Wei Han, Wen Bao, Jie Lu

Abstract

Peroxisome proliferator-activated receptor alpha (PPARA) is the molecular target of fibrates commonly used to treat dyslipidemia and diabetes. Recently, the potential role of PPARA in other pathological conditions, such as cancers, has been recognized. Here, using bioinformatics analysis, we found that PPARA was expressed at relatively low levels in pancancers, and Kaplan-Meier analyses revealed that high PPARA protein expression was correlated with better survival of patients with colon cancer. In vitro experiments showed that fenofibrate regulated cell cycle distribution, promoted apoptosis, and suppressed cell proliferation and epithelial mesenchymal transition by activating PPARA. PPARA activation inhibited DNMT1 activity and abolished methylation-mediated CDKN2A repression. Downregulation of cyclin-CDK complexes led to the restoration of CDKN2A, which caused cell cycle arrest in the G1 phase via regulation of the CDKN2A/RB/E2F pathway. Finally, we demonstrated that fenofibrate administration inhibited tumor growth and DNMT1 activity in vivo. The PPARA agonist, fenofibrate, might serve as an applicable agent for epigenetic therapy of colon cancer patients.

Substances (14)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Fenofibrate 49562-28-9 C20H21ClO4 784 suppliers $5.00-$602.00
Fenofibrate 49562-28-9 C20H21ClO4 784 suppliers $5.00-$602.00
Fenofibrate 49562-28-9 C20H21ClO4 784 suppliers $5.00-$602.00
Fenofibrate 49562-28-9 C20H21ClO4 784 suppliers $5.00-$602.00
Fenofibrate 49562-28-9 - Inquiry
Fenofibrate 49562-28-9 - Inquiry
Fenofibrate 49562-28-9 C20H21ClO4 - Inquiry
Fenofibrate 49562-28-9 C20H21ClO4 - Inquiry
Fenofibrate 49562-28-9 - Inquiry
Fenofibrate 49562-28-9 - Inquiry

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