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

• Published in: BMB Reports Vol. 45; no. 12; pp. 724 - 729
• Main Authors: Kim, H.E., Chonnam National University, Gwangju, Republic of Korea, Ishihara, Atsushi, Tottori University, Tottori, Japan, Lee, S.G., Chonnam National University, Gwangju, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology - BMB Reports 01.12.2012; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: alpha-MSH; alpha-MSH - pharmacology; Animals; Caffeic Acids; Caffeic Acids - chemistry; Caffeic Acids - pharmacology; Caffeoylserotonin; Caffeoylserotonin; Cyclic AMP; ERK; Melanogenesis; MITF; Cell Differentiation; Cell Differentiation - drug effects; Cell Line, Tumor; Cyclic AMP; Cyclic AMP - metabolism; Down-Regulation; Down-Regulation - drug effects; Enzyme Activation; Enzyme Activation - drug effects; ERK; Extracellular Signal-Regulated MAP Kinases; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids; Flavonoids - pharmacology; Melanogenesis; MELANOMA; Melanoma, Experimental; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; MELANOME; Mice; Microphthalmia-Associated Transcription Factor; Microphthalmia-Associated Transcription Factor - metabolism; MITF; Monophenol Monooxygenase; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; Oxidoreductases; Oxidoreductases - metabolism; Phosphorylation; Serotonin; Serotonin - analogs & derivatives; Serotonin - chemistry; Serotonin - pharmacology; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/bmbrep.2012.45.12.039

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 MITE, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphotylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on alpha-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.