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Int. J. Mol. Sci. 2017, 18(6), 1213; doi:10.3390/ijms18061213

Depigmenting Effect of Resveratrol Is Dependent on FOXO3a Activation without SIRT1 Activation

College of Medicine, Seoul National University, Seoul National University Bundang Hospital, Gyeonggi 13620, Korea
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 29 March 2017 / Revised: 27 May 2017 / Accepted: 30 May 2017 / Published: 7 June 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Resveratrol exhibits not only anti-melanogenic property by inhibiting microphthalmia-associated transcription factor (MITF), but also anti-aging property by activating sirtuin-1 (SIRT1). In this study, the relationship between depigmenting effect of resveratrol and SIRT1/forkhead box O (FOXO) 3a activation and was investigated. Resveratrol suppressed melanogenesis by the downregulation of MITF and tyrosinase via ERK pathway. Results showed that the expression of both SIRT1 and FOXO3a were increased. It is reported that SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. However in our study, FOXO3a activation appeared earlier than that of SIRT1. Furthermore, the effect of resveratrol on the levels of MITF and tyrosinase was suppressed when melanocytes were pre-treated with SP600125 (JNK inhibitor). However, pre-treatment with SIRT1 inhibitor (EX527, or sirtinol) did not affect the levels of MITF and tyrosinase. Therefore, resveratrol inhibits melanogenesis through the activation of FOXO3a but not by the activation of SIRT1. Although SIRT1 activation by resveratrol is a well-known mechanism of resveratrol-induced antiaging effects, our study showed that not SIRT1 but FOXO3a activation is involved in depigmenting effects of resveratrol. View Full-Text
Keywords: extracellular signal-regulate kinase; forkhead box O; melanogenesis; resveratrol; sirtuin-1 extracellular signal-regulate kinase; forkhead box O; melanogenesis; resveratrol; sirtuin-1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kwon, S.-H.; Choi, H.-R.; Kang, Y.-A.; Park, K.-C. Depigmenting Effect of Resveratrol Is Dependent on FOXO3a Activation without SIRT1 Activation. Int. J. Mol. Sci. 2017, 18, 1213.

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