Nicotinic acid hydroxamate downregulated the melanin synthesis and tyrosinase activity through activating the MEK/ERK and AKT/GSK3β signaling pathways.

In this study, nicotinic acid hydroxamate (NAH), a nicotinic acid derivative, was found to show dose-dependent inhibition of melanin content and tyrosinase activity of murine melanoma B16F10 cells with or without being cotreated with cAMP stimulators. In the studies on signaling pathways for skin whitening, NAH-treated B16F10 cells resulted in a decrease in the expression of tyrosinase, tyrosinase-related protein-1, and microphthalmia-associated transcription factor (MITF). PD98059 and LY294002 additions were obviously to increase melanin contents in B16F10 cells; however, they were reversed by NAH cotreatments. NAH-mediated increases in the phosphorylation of mitogen-activated protein kinase kinase (MEK)/ERK and AKT/glycogen synthase kinase-3β (GSK3β) were also found, which in turn led to the inhibition of MITF expression and then downregulated tyrosinase and tyrosinase-related protein (TRP)-1 expressions. These results suggest that NAH may be an active component in the inhibition of melanogenesis, which will have potential uses as cosmetics for whitening and need further investigation.