title: Cyclohexanediol bis-ethylhexanoate inhibits melanogenesis of murine B16 melanoma and UV-induced pigmentation in human skin.
abstract: The role of cyclohexane diester analogues in the formation of melanin has been recently reported. In the present study, we investigated the inhibitory effect of cyclohexanediol bis-ethylhexanoate (CHEH) on melanogenesis in B16 melanoma cells and on UV-B-induced pigmentation in human skin. CHEH significantly reduced the melanin content in a dose-dependent manner, without cytotoxic effects at the effective concentrations. Moreover, CHEH dose-dependently inhibited tyrosinase activity in B16 melanoma cells, as confirmed by Western blot analysis of the tyrosinase protein levels. However, tyrosinase transcript levels remained unchanged under the same experimental conditions. These results indicate that CHEH inhibited melanogenesis in B16 melanoma cells by regulating tyrosinase activity at the post-transcriptional level. On the other hand, in a cell-free system, CHEH did not inhibit tyrosinase activity. This indicated that CHEH suppressed the pigmentation of melanocytes by indirectly regulating tyrosinase activity. Finally, in a clinical trial, a cream containing 1.0% CHEH showed good whitening effect on UV-induced pigmented human skin without adverse effects. In conclusion, we suggest that CHEH may be an effective inhibitor of melanogenesis and useful effects in the treatment of hyperpigmented disorders.
authors.affiliation: Woongjin Coway Cosmetics R&D Center, Gasan-dong, Geumcheon-gu, Seoul 153–803, Korea.
authors.forename: Joo Hyuck
authors.initials: JH
authors.lastname: Lim
authors.forename: So-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Myoung Rae
authors.initials: MR
authors.lastname: Kim
authors.forename: Byoung-Sam
authors.initials: BS
authors.lastname: Yoo
authors.forename: Jae Chan
authors.initials: JC
authors.lastname: Yang
authors.forename: In Woo
authors.initials: IW
authors.lastname: Cheong
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Hun
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000818:Animals; D002208:Caproates / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007370:Interferon Type I / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics; D011257:Pregnancy Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D002208:Caproates; D003510:Cyclohexanes; D007370:Interferon Type I; D008543:Melanins; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C582952:cyclohexanediol bis-ethylhexanoate; C020947:interferon tau; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C079237:ethyl hexanoate