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
In this study, we evaluated the anti-melanogenesis effects ofCaffeoylserotonin (CaS) in B16 melanoma cells. Treatment withCaS reduced the melanin content and tyrosinase (TYR) activity inB16 melanoma cells in a dose-dependent manner. CaS inhibitedthe expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, andtyrosinase-related protein-1 (TRP-1), but not TRP-2. α-MSH isknown to interact with melanocortin 1 receptor (MC1R) thusactivating adenylyl cyclase and increasing intracellular cyclicAMP (cAMP) levels. Furthermore, cAMP activates extracellularsignal-regulated kinase 2 (ERK2) via phosphorylation, whichphosphorylates MITF, thereby targeting the transcription factor toproteasomes for degradation. The CaS reduced intracellularcAMP levels to unstimulated levels and activated ERK phosphorylationwithin 30 min. The ERK inhibitor PD98059 abrogatedthe suppressive effect of CaS on α-MSH-induced melanogenesis.Based on this study, the inhibitory effects of CaS on melanogenesisare derived from the downregulation of MITF signaling viathe inhibition of intracellular cAMP levels, as well as accelerationof ERK activation.