Hypopigmentary Action of Dihydropyranocoumarin D2, a Decursin Derivative, as a MITF-Degrading Agent

초록

In this study, the decursin derivative dihydropyranocoumarin D2 (1) was selected for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). The results showed that I effectively inhibited melanin synthesis in a concentration-dependent manner, but that it did not inhibit tyrosinase in a cell-free system. In addition, the changes in ERK, Akt, and microphthalmia-associated transcription factor (MITF) in response to treatment with I were assessed. The results revealed that ERK was dramatically up-regulated and MITF was down-regulated in response to treatment with I, but that Akt was unchanged. Therefore, the effects of I on melanogenesis were examined in the absence or presence of PD98059 (a specific inhibitor of the ER K pathway). PD98059 restored hypopigmentation and the down-regulation of MITF induced by I. Finally, MITF down-regulation by I was clearly restored by both chloroquine, a lysosomal proteolysis inhibitor, and MG132, a proteasome inhibitor.

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