NAD(P)H dehydrogenase, quinone 1 (NQO1), protects melanin‐producing cells from cytotoxicity of rhododendrol. (4th March 2016)

• Record Type: Journal Article
• Authors: Okubo, Ayaka; Yasuhira, Shinji; Shibazaki, Masahiko; Takahashi, Kazuhiro; Akasaka, Toshihide; Masuda, Tomoyuki; Maesawa, Chihaya
• Is Part Of: Pigment cell & melanoma research. Volume 29:Number 3(2016:May)
• Page Start: 309
• Page End: 316
• Publication Date: 2016-03-04
• Subjects: rhododendrol -- quinone -- NQO1 -- melanin -- carnosic acid; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12461
• Languages: English
• ISSNs: 1755-1471

Abstract

Summary: Rhododendrol (RD) is a potent tyrosinase inhibitor that is metabolized to RD‐quinone by tyrosinase, which may underlie the cytotoxicity of RD and leukoderma of the skin that may result. We have examined how forced expression of the NAD(P)H quinone dehydrogenase, quinone 1 (NQO1), a major quinone‐reducing enzyme in cytosol, affects the survival of RD‐treated cells. We found that treatment of the mouse melanoma cell line B16BL6 or normal human melanocytes with carnosic acid, a transcriptional inducer of the NQO1 gene, notably suppressed the cell killing effect of RD. This effect was mostly abolished by ES936, a highly specific NQO1 inhibitor. Moreover, conditional overexpression of the human NQO1 transgene in B16BL6 led to an expression‐dependent increase of cell survival after RD treatment. Our results suggest that NQO1 attenuates the cytotoxicity of RD and/or its metabolites.