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

Kaneda, Toshio and Matsumoto, Misaki and Sotozono, Yayoi and Fukami, Satoshi and Nugroho, Alfarius Eko and Hirasawa, Yusuke and A. Hadi, A. Hamid and Morita, Hiroshi (2019) 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. Journal of Natural Medicines, 73 (1). pp. 47-58. ISSN 1340-3443

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Official URL: https://doi.org/10.1007/s11418-018-1233-7

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.

Item Type: Article
Uncontrolled Keywords: Garcinia; Triterpenoids; Cycloartane; Melanoma; MITF; β-Catenin; ERK; c-Raf
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions: Faculty of Science > Dept of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 18 Jan 2019 01:35
Last Modified: 18 Jan 2019 01:35
URI: http://eprints.um.edu.my/id/eprint/20058

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