title: NAD(P)H dehydrogenase, quinone 1 (NQO1), protects melanin-producing cells from cytotoxicity of rhododendrol.
abstract: 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.
authors: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Shiwa-gun, Japan.
authors: Ayaka
authors: A
authors: Okubo
authors: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Shiwa-gun, Japan.
authors: Shinji
authors: S
authors: Yasuhira
authors: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Shiwa-gun, Japan.
authors: Masahiko
authors: M
authors: Shibazaki
authors: Department of Dermatology, School of Medicine, Iwate Medical University, Morioka, Japan.
authors: Kazuhiro
authors: K
authors: Takahashi
authors: Department of Dermatology, School of Medicine, Iwate Medical University, Morioka, Japan.
authors: Toshihide
authors: T
authors: Akasaka
authors: Department of Pathology, School of Medicine, Iwate Medical University, Shiwa-gun, Japan.
authors: Tomoyuki
authors: T
authors: Masuda
authors: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Shiwa-gun, Japan.
authors: Chihaya
authors: C
authors: Maesawa
mesh_terms: D045784:Abietanes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000440:Butanols / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D007210:Indoleacetic Acids / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D045784:Abietanes; D000440:Butanols; D007210:Indoleacetic Acids; D008543:Melanins; C115945:rhododendrol; D016660:NAD(P)H Dehydrogenase (Quinone); C018381:salvin
keywords: NQO1; carnosic acid; melanin; quinone; rhododendrol