{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:12:06Z","timestamp":1790741526890,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T00:00:00Z","timestamp":1403740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Rhododendrol, an inhibitor of melanin synthesis developed for lightening\/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up\u2010regulation of the <jats:styled-content style=\"fixed-case\">CCAAT<\/jats:styled-content>\u2010enhancer\u2010binding protein homologous protein gene responsible for apoptosis and\/or autophagy and caspase\u20103 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase\u2010dependent accumulation of <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress and\/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.<\/jats:p>","DOI":"10.1111\/pcmr.12269","type":"journal-article","created":{"date-parts":[[2014,5,29]],"date-time":"2014-05-29T09:03:17Z","timestamp":1401354197000},"page":"754-763","source":"Crossref","is-referenced-by-count":117,"title":["Rhododendrol, a depigmentation\u2010inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase\u2010dependent mechanism"],"prefix":"10.1111","volume":"27","author":[{"given":"Minoru","family":"Sasaki","sequence":"first","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Sato","sequence":"additional","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Umeda","sequence":"additional","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Kawabata","sequence":"additional","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yamagata University School of Medicine Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Innovative Beauty Science Laboratory Kanebo Cosmetics Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64020825.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2004.00130.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8019.2001.014001029.x"},{"key":"e_1_2_7_5_1","first-page":"407","volume-title":"Modern Methods of Organic Synthesis","author":"Carruthers W.","year":"1978"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00802.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26226"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/1046-199X(95)90112-4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.44.1033"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1539\/joh.40.118"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1539\/joh.40.137"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01250a010"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.70680"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00213.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.214"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi1947.98.1_41"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)90451-2"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/4193"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050769"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-0960.1996.tb01014.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(72)90173-7"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi011535n"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0021-9258(18)96973-5","article-title":"The tyrosine hydroxylase activity of mammalian tyrosinase","volume":"241","author":"Pomerantz S.H.","year":"1966","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2011.576010"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.181"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0216com"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.16"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1999.tb00756.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00836.x"}],"container-title":["Pigment Cell &amp; Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12269","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12269","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pcmr.12269","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T15:54:00Z","timestamp":1695570840000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,26]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1111\/pcmr.12269"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12269","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,26]]}}}