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Dual effects of acetylsalicylic acid on ERK signaling and Mitf transcription lead to inhibition of melanogenesis

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Abstract

Acetylsalicylic acid (ASA) is widely used as an analgesic/antipyretic drug. It exhibits a wide range of biological effects, including preventative effects against heart attack and stroke, and the induction of apoptosis in various cancer cells. We previously found that ASA inhibits melanogenesis in B16 melanoma cells. However, the mechanisms of how ASA down-regulates melanin synthesis remain unclear. Here, we investigated the effect of ASA on melanogenic pathways, such as extracellular signal-regulated kinase (ERK) and microphthalmia-associated transcription factor (Mitf) transcription. ASA significantly inhibited melanin synthesis in a dose-dependent manner without oxidative stress and cell death. Semi-quantitative reverse transcription-polymerase chain reaction analysis showed that the inhibitory effect of ASA might be due to the inhibition of Mitf gene transcription. Interestingly, ASA also induced ERK phosphorylation. Additionally, treatment with PD98059, a specific ERK phosphorylation inhibitor, abolished the anti-melanogenic effect of ASA. These results suggest that the depigmenting effect of ASA results from down-regulation of Mitf, which is induced by both the induction of ERK phosphorylation and the inhibition of Mitf transcription.

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Acknowledgments

This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number 25740018.

Author contributions

T.N. and K.S. designed the experiments; T.N., M.U., M.A., S.S., and K.S. performed the experiments; T.N. and K.S. analyzed the data. K.S. wrote this paper.

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Authors and Affiliations

  1. Graduate School of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan

    Takashi Nishio & Kazuomi Sato

  2. Department of Life Science, College of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan

    Mai Usami, Mizuki Awaji, Sumire Shinohara & Kazuomi Sato

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  1. Takashi Nishio
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Correspondence to Kazuomi Sato.

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Nishio, T., Usami, M., Awaji, M. et al. Dual effects of acetylsalicylic acid on ERK signaling and Mitf transcription lead to inhibition of melanogenesis. Mol Cell Biochem 412, 101–110 (2016). https://doi.org/10.1007/s11010-015-2613-x

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