Theophylline enhances melanogenesis in B16F10 murine melanoma cells through the activation of the MEK 1/2, and Wnt/β-catenin signaling pathways

Theophylline is a kind of methyl xanthine, which has been suggested to inhibit the activity of phosphodiesterase and increase the intracellular level of cyclic adenine monophosphate (cAMP). Theophylline has also been reported to increase the length and complexity of the dendritic process in melanocytes. However, the mode of action of theophylline in melanogenesis has never been reported. In this study, the effects of theophylline on melanogenesis were evaluated spectrophotometrically by the mushroom tyrosinase activity assay and by the determination of the intracellular tyrosinase activity and melanin content. The expression levels of melanogenesis-related proteins were analyzed by Western blot. The results indicated that theophylline (100-500 mu M) effectively enhanced melanogenesis in the B16F10 murine melanoma cells. Moreover, theophylline increased the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 (TRP-1), and the level of phosphorylated extracellular regulated protein kinase (p-ERK) and phosphorylated glycogen synthase kinase-3 beta (p-GSK3 beta) were also increased. In summary, the results revealed that theophylline promoted melanogenesis in B16F10 cells by upregulating the mitogen-activated protein kinase kinase 1 (MEK 1/2) and Wnt/beta-catenin signaling pathways.