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Rhododendrol, a depigmentation‐inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase‐dependent mechanism
Author(s) -
Sasaki Minoru,
Kondo Masatoshi,
Sato Kohji,
Umeda Mai,
Kawabata Keigo,
Takahashi Yoshito,
Suzuki Tamio,
Matsunaga Kayoko,
Inoue Shintaro
Publication year - 2014
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.12269
Subject(s) - tyrosinase , cytotoxicity , melanocyte , melanin , chemistry , depigmentation , biochemistry , microbiology and biotechnology , enzyme , biology , in vitro , cancer research , melanoma , genetics
Summary 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 RNA . 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‐regulation of the CCAAT ‐enhancer‐binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase‐3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase‐dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.