Interaction of NADPH oxidase and aryl hydrocarbon receptor in melanogenesis by B16/F10 cell line

Vitiligo, psoriasis and some skin cancers are due to abnormal melanogenesis and disturbance in melanocytes homeostasis. Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional factor involved in many physiological processes including drugs metabolism, development of immune system, cellular homeostasis, regulation of cell cycle, and as an essential factor in melanogenesis. The aim of this study was to investigate whether the NADPH oxidases (NOXs) system can interfere with the normal function of aryl hydrocarbon receptor in melanogenesis.

B16/F10 mouse melanoma cell line were cultured in DMEM and treated with different concentrations of the endogenous ligand of AHR, 6-formylindolo[3,2-b] carbazole (FICZ) (1-100 nM) alone or in combination with an AHR antagonist 3'-Methoxy-4'-Nitroflavone, MNF, or cytochrome P450 type CYP1A1 inhibitor, or a NADPH oxidase (NOX) inhibitor, curcumin (1µM), for different time periods. The activity of CYP1A1 and tyrosinase enzymes as well as total melanin level were measured at the end of treatments.

CYP1A1 enzyme activity was induced in B16/F10 cells by FICZ in a dose and time dependent manner. Tyrosinase activity and melanin level also were increased by FICZ 100nM. Importantly, treatment of the cells with combination of FICZ 1nM and curcumin induced melanin synthesis.

Taken together, inhibition of metabolic degradation of FICZ might elicit biological/toxicological effects on skin homeostasis.