Abstract
Imatinib mesylate is a targeted anti-cancer drug with skin pigmentation as a side effect. The action mechanism of imatinib mesylate on melanogenesis remains unclear. The purpose of this study was to elucidate the mechanism of imatinib mesylate on melanogenesis associated with the microphthalmia-associated transcription factor (MITF) signaling pathway in murine melanoma cells. This study revealed that imatinib mesylate increased tyrosinase activity but decreased hydrogen peroxide generation in B16F1 cells. Additionally, imatinib mesylate at 0.3-5 μM was nontoxic to the cells and promoted melanin production. Moreover, imatinib mesylate at 5 μM increased the expression levels of TRP-2 and p38 related to melanogenesis compared with the blank group in western blot and immunofluorescence staining analyses. The expression level of p-MITF in the nucleus was increased in the presence of imatinib mesylate compared with the blank group. These results suggest that imatinib mesylate could promote melanogenesis through the modulation of p38 and MITF.