title: Depigmentation of α-melanocyte-stimulating hormone-treated melanoma cells by β-mangostin is mediated by selective autophagy.
abstract: Melanogenesis is a key pathway for the regulation of skin pigmentation and the development of skin-lightening/skin-whitening drugs or cosmetics. In this study, we found that β-mangostin from seedcases of Garcinia mangostana inhibited α-melanocyte-stimulating hormone (α-MSH)-mediated melanogenesis in B16F10 melanoma cells and a three-dimensional human skin model. β-Mangostin significantly inhibited the protein level of tyrosinase induced by α-MSH in UPS (ubiquitin proteasome system)-independent and lysosome-dependent manner. The inhibition of autophagy by 3-methyladenine treatment or ATG5 knockdown effectively recovered premelanosome protein as well as tyrosinase degraded by the β-mangostin treatment. However, rapamycin, a representative non-selective autophagy inducer, triggered autophagy in α-MSH-stimulated cells, which was characterized by a considerable decrease in p62, but it was unable to inhibit melanogenesis. Melanosome-engulfing autophagosomes were observed using transmission electron microscopy. Furthermore, previously formed melanin could be degraded effectively in an autophagy-dependent manner in β-mangostin-treated cells. Taken together, our results suggest that β-mangostin inhibits the melanogenesis induced by α-MSH via an autophagy-dependent mechanism, and thus, the depigmentation effect of β-mangostin may depend on autophagy targeted at the melanosome rather than non-selective autophagy.
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, KRIBB, Cheongwon, Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.
authors.forename: Sang-Seok
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.
authors.forename: Soojong
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Madhi
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.
authors.forename: Ki-Hun
authors.initials: KH
authors.lastname: Park
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Korea.|PMBBRC, Gyeongsang National University, Jinju, Korea.
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy; D002470:Cell Survival; D029762:Garcinia mangostana; D006801:Humans; D007249:Inflammation; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology; D008545:Melanoma / Q000378:metabolism*; D008546:Melanoma, Experimental; D020460:Melanosomes / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation; D010936:Plant Extracts / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D008543:Melanins; D010936:Plant Extracts; D025801:Ubiquitin; D044004:Xanthones; C025946:3-methyladenine; D000521:alpha-MSH; D014442:Monophenol Monooxygenase; D046988:Proteasome Endopeptidase Complex; D000225:Adenine; C021053:mangostin
keywords: autophagy; melanogenesis; α-melanocyte-stimulating hormone; β-mangostin