title: Different effects of five depigmentary compounds, rhododendrol, raspberry ketone, monobenzone, rucinol and AP736 on melanogenesis and viability of human epidermal melanocytes.
abstract: Numerous medications are used to treat hyperpigmentation. However, several reports have indicated that repeated application of some agents, such as rhododendrol (RD), raspberry ketone (RK) and monobenzone (MB), can be toxic to melanocytes. Although these agents had severe side effects in human trials, no current in vitro methods can predict the safety of such drugs. This study assessed the in vitro effects of five depigmentary compounds including leukoderma-inducing agents. In particular, we determined the effects of different concentrations and exposure times of different depigmentary agents on cell viability and melanogenesis in the presence and absence of ultraviolet B (UVB) radiation. Concentrations of RD, RK and MB that inhibit melanogenesis are similar to concentrations that are cytotoxic; however, concentrations of rucinol (RC) and AP736 that inhibit melanogenesis are much lower than concentrations that are cytotoxic. Furthermore, the concentrations that cause toxic effects depend on exposure duration, and prolonged exposure to RD, RK and MB had more cytotoxic effects than prolonged exposure to RC and AP736. The cytotoxic effects of RD and RK appear to be mediated by apoptosis due to increased expression of caspase-3 and caspase-8; UVB radiation increased the cytotoxicity of these agents and also increased caspase activity. Our results indicate that different leukoderma-inducing compounds have different effects on the viability of normal epidermal melanocytes and suggest that the in vitro assay used here can be used to predict whether an investigational compound that induces leukoderma may lead to adverse effects in human trials.
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Chang Seok
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Yung Hyup
authors.initials: YH
authors.lastname: Joo
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Heung Soo
authors.initials: HS
authors.lastname: Baek
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Park
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Nok-Hyun
authors.initials: NH
authors.lastname: Park
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: John Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Song Seok
authors.initials: SS
authors.lastname: Shin
authors.affiliation: Amorepacific Co. R&D center, Yongin, Korea.
authors.forename: Hae-Kwang
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry; D017209:Apoptosis; D001549:Benzamides / Q000737:chemistry*; D000440:Butanols / Q000737:chemistry*; D002074:Butanones / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry*; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis; D010858:Pigmentation; D012118:Resorcinols / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: C508220:4-n-butylresorcinol; C000592311:5-adamantan-1-yl-N-(2,4-dihydroxybenzyl)-2,4-dimethoxybenzamide; D001549:Benzamides; D000440:Butanols; D002074:Butanones; D006873:Hydroquinones; D008543:Melanins; D012118:Resorcinols; C115945:rhododendrol; C035522:raspberry ketone; C006429:monobenzone; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D000218:Adamantane
keywords: cell viability; chemical leukoderma; depigmentary agent; melanocyte