Abstract: Objective To get more insight on the molecular mechanisms involved in psoralen induced melanogenesis during repigmentation of the hypomelanotic lesions of vitiligo vulgaris under PUVA treatment. Methods The effects of various concentrations of 8-methoxypsoralen (8-MOP)(10～500μmol/L) upon cellular morphologic changes, tyrosinase activity, and melanin contents of cultured B16F10 murine melanoma cells were examined in vitro. Results 8-MOP caused a striking change in cellular morphology with many elongate cell dendrites and deposits of brown granular materials in cytoplasm, these effects were observed clearly at final concentrations between 50 and 100μmol/L of 8-MOP after treating for 48 hours. In a range of final concentrations(10～500μmol/L), there were a dose-dependent stimulation of tyrosinase activity and melanin contents with a 2～3 fold increase over untreated cells (P<0.01), the maximum action was obtained at 50 and 100μmol/L. It was also found that there was a dose related inhibition of cell growth with a 60% reduction of growth at a final concentration of 100μmol/L and no growth of cells at the concentration of 500μmol/L. Furthermore, isobutyl methylxanthine(IBMX), a protein kinase A (PKA) activator, potentiated the 8-MOP upregulation of tyrosinase activity and melanin contents, however, 12-O tetradecanoyl phorbol 13-acetate (TPA),a potent activator of PKC, inhibited the upregulative effect of 8-MOP when treated for a long duration. Conclusion These results demonstrate that in murine melanoma cells 8-MOP could induce melanogenesis by increasing tyrosinase activity and melanin contents. At least, PKA and PKC-dependent signaling pathways appear to play an important role in the melanogenic effect of 8-MOP.

Key words: Methoxsalen, Melanin, Signal transduction