{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:16:13Z","timestamp":1790388973267,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,1,29]],"date-time":"2017-01-29T00:00:00Z","timestamp":1485648000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26461705"],"award-info":[{"award-number":["26461705"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content><\/jats:italic>\u20104\u2010(4\u2010Hydroxyphenyl)\u20102\u2010butanol (rhododendrol, <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>), a skin\u2010whitening agent, is known to induce leukoderma in some people. To explore the mechanism underlying this effect, we previously showed that the oxidation of <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> with mushroom or human tyrosinase produces cytotoxic quinone oxidation products. We then examined the metabolism of <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> in B16F1 melanoma cells in\u00a0vitro and detected <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>\u2010pheomelanin and <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>\u2010quinone bound to non\u2010protein and protein thiols. In this study, we examined the changes in glutathione (<jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>) and cysteine in B16 cells exposed to <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> for up to 24\u00a0h. We find that the levels of cysteine, but not those of <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>, decrease during 0.5\u2010 to 3\u2010h exposure, due to oxidation to cystine. This pro\u2010oxidant activity was then examined using synthetic melanins. Indeed, we find that <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>\u2010eumelanin exerts a pro\u2010oxidant activity as potent as Dopa\u2010pheomelanin. <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>, cysteine, ascorbic acid, and <jats:styled-content style=\"fixed-case\">NADH<\/jats:styled-content> were oxidized by <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>\u2010eumelanin with a concomitant production of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. We propose that <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>\u2010eumelanin induces cytotoxicity through its potent pro\u2010oxidant activity.<\/jats:p>","DOI":"10.1111\/pcmr.12556","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T15:08:58Z","timestamp":1478358538000},"page":"63-67","source":"Crossref","is-referenced-by-count":20,"title":["The potent pro\u2010oxidant activity of rhododendrol\u2013eumelanin induces cysteine depletion in B16 melanoma cells"],"prefix":"10.1111","volume":"30","author":[{"given":"Shosuke","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masae","family":"Okura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Dermatology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,29]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.10.011"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(87)80197-4"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.04.008"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12275"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12300"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12363"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2014.07.001"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18447"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2016.02.003"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12494"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12365591"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11624"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12262"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.07.010"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12199"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12269"},{"key":"e_1_2_4_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2012.01011.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.12556","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12556","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12556","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T14:12:01Z","timestamp":1695564721000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/pcmr.12556"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12556","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]}}}