Fenofibrate suppresses melanogenesis in B16-F10 melanoma cells via activation of the p38 mitogen-activated protein kinase pathway.

Fenofibrate suppresses melanogenesis in B16-F10 melanoma cells via activation of the p38 mitogen-activated protein kinase pathway.
Chem Biol Interact. 2013 Jul 18;
Authors: Huang YC, Liu KC, Chiou YL, Yang CH, Chen TH, Li TT, Liu LL
Abstract
Fenofibrate and ciglitazone belong to the classes of fibrates and thiazolidinediones, respectively. Their pharmacological actions on peroxisome proliferator-activated receptors (PPARs) present a potential therapy for hyperlipidemia and hyperglycemia. However, the melanogenesis affected by PPAR ligands in melanocytes has not been well investigated. By determining the melanin content of cells treated with PPAR agonists, we showed that fenofibrate significantly reduced melanin synthesis, but its major active metabolite, fenofibric acid, did not. Notably, the suppression of melanogenesis by fenofibrate could not be prevented by the PPARα specific antagonist GW6471. In addition, T0901317, a liver X receptor (LXR) agonist, restored the antimelanogenic activity of fenofibrate. Accordingly, fenofibrate may suppress melanogenesis through a PPARα-independent pathway. Treatment of cells with fenofibrate led to the down-regulated gene expression of melanocortin 1 receptor (MC1R). Fenofibrate also attenuated the dihydroxyphenylalanine (DOPA)-staining activity and expression of tyrosinase as well as the expression of microphthalmia-associated transcription factor (MITF). The phosphorylation of p38 mitogen-activated pr...

Source: Chemico-Biological Interactions - July 18, 2013 Category: Molecular Biology Authors: Huang YC, Liu KC, Chiou YL, Yang CH, Chen TH, Li TT, Liu LL Tags: Chem Biol Interact Source Type: research