title: The effects of Caffeoylserotonin on inhibition of melanogenesis through the downregulation of MITF via the reduction of intracellular cAMP and acceleration of ERK activation in B16 murine melanoma cells.
abstract: In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia- associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. α-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on α-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation.
authors.affiliation: Department of Biotechnology, Bioenergy Research Center, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Kim
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishihara
authors.forename: Seong-Gene
authors.initials: SG
authors.lastname: Lee
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010766:Phosphorylation; D012701:Serotonin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D002109:Caffeic Acids; D005419:Flavonoids; D051739:Microphthalmia-Associated Transcription Factor; C534691:N-caffeoylserotonin; D012701:Serotonin; D000521:alpha-MSH; D000242:Cyclic AMP; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one