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Open Access 01-01-2019 | Original Paper

Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf–MEK1–ERK signaling axis

Authors: Toshio Kaneda, Misaki Matsumoto, Yayoi Sotozono, Satoshi Fukami, Alfarius Eko Nugroho, Yusuke Hirasawa, Hadi A. Hamid A, Hiroshi Morita

Published in: Journal of Natural Medicines | Issue 1/2019

Abstract

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.

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Title: Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf–MEK1–ERK signaling axis
Authors: Toshio Kaneda
Misaki Matsumoto
Yayoi Sotozono
Satoshi Fukami
Alfarius Eko Nugroho
Yusuke Hirasawa
Hadi A. Hamid A
Hiroshi Morita
Publication date: 01-01-2019
Publisher: Springer Singapore
Published in: Journal of Natural Medicines / Issue 1/2019
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-018-1233-7

ACC 2024 Congress

Springer Medicine

Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf–MEK1–ERK signaling axis

Abstract

ACC 2024 Congress

Springer Medicine

Abstract

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