We recently reported that (23R, 24E)-23-acetoxymangiferonic
acid (23R-AMA), a
cycloartane triterpenoid isolated by activity-guided separation from a
methanol extract of Garcinia sp. bark, inhibited
melanin production via inhibition of
tyrosinase (TYR) expression in the B16-F10
melanoma cell line. Since 23R-AMA also inhibited
microphthalmia-associated transcription factor (MITF) expression, an upstream factor of TYR, these features of 23R-AMA were thought to be appropriate for development of whitening
cosmetics. However, 23R-AMA exhibited growth inhibition other than inhibition of
melanin production in B16-F10 cells. Therefore, we investigated
biological activities of 23R-AMA in detail, focused on its application as an anti-
melanoma compound. In this study, we demonstrated that 23R-AMA inhibited cell proliferation and basic FGF (bFGF)-induced migration in B16-F10 cells. Furthermore, 23R-AMA promoted ser45/thr41 phosphorylation of β-
catenin and suppressed its intranuclear accumulation, which was suggested to be related to inhibition of MITF expression. The transcriptional activity of MITF is known to be regulated by phosphorylation via activated ERK. Further investigation revealed that 23R-AMA inhibited phosphorylation of c-Raf, MEK-1, and ERK, and also that of upstream molecules including FAK and c-Src. These results suggested that 23R-AMA inhibited growth and migration of B16-F10
melanoma by regulating both MITF expression and its activity. The activities of 23R-AMA reported in this study are new aspects of
cycloartane triterpenoids.