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The potent pro‐oxidant activity of rhododendrol–eumelanin induces cysteine depletion in B16 melanoma cells
Author(s) -
Ito Shosuke,
Okura Masae,
Wakamatsu Kazumasa,
Yamashita Toshiharu
Publication year - 2017
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12556
Subject(s) - glutathione , chemistry , cysteine , cysteamine , ascorbic acid , pro oxidant , cystine , cytotoxicity , biochemistry , tyrosinase , melanin , reactive oxygen species , in vitro , thiol , quinone , enzyme , food science
Summary RS ‐4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD ), a skin‐whitening agent, is known to induce leukoderma in some people. To explore the mechanism underlying this effect, we previously showed that the oxidation of RD with mushroom or human tyrosinase produces cytotoxic quinone oxidation products. We then examined the metabolism of RD in B16F1 melanoma cells in vitro and detected RD ‐pheomelanin and RD ‐quinone bound to non‐protein and protein thiols. In this study, we examined the changes in glutathione ( GSH ) and cysteine in B16 cells exposed to RD for up to 24 h. We find that the levels of cysteine, but not those of GSH , decrease during 0.5‐ to 3‐h exposure, due to oxidation to cystine. This pro‐oxidant activity was then examined using synthetic melanins. Indeed, we find that RD ‐eumelanin exerts a pro‐oxidant activity as potent as Dopa‐pheomelanin. GSH , cysteine, ascorbic acid, and NADH were oxidized by RD ‐eumelanin with a concomitant production of H 2 O 2 . We propose that RD ‐eumelanin induces cytotoxicity through its potent pro‐oxidant activity.