title: Wnt/β-catenin signaling inhibitor ICG-001 enhances pigmentation of cultured melanoma cells.
abstract: BACKGROUND
  Wnt/β-catenin signaling is important in development and differentiation of melanocytes.
  
  
  OBJECTIVE
  The object of this study was to evaluate the effects of several Wnt/β-catenin signaling inhibitors on pigmentation using melanoma cells.
  
  
  METHODS
  Melanoma cells were treated with Wnt/β-catenin signaling inhibitors, and then melanin content and tyrosinase activity were checked.
  
  
  RESULTS
  Although some inhibitors showed slight inhibition of pigmentation, we failed to observe potential inhibitory effect of those chemicals on pigmentation of HM3KO melanoma cells. Rather, one of powerful Wnt/β-catenin signaling inhibitors, ICG-001, increased the pigmentation of HM3KO melanoma cells. Pigmentation-enhancing effect of ICG-001 was reproducible in other melanoma cell line MNT-1. Consistent with these results. ICG-001 increased the expression of pigmentation-related genes, such as MITF, tyrosinase and TRP1. When ICG-001 was treated, the phosphorylation of CREB was significantly increased. In addition, ICG-001 treatment led to quick increase of intracellular cAMP level, suggesting that ICG-001 activated PKA signaling. The blockage of PKA signaling with pharmaceutical inhibitor H89 inhibited the ICG-001-induced pigmentation significantly.
  
  
  CONCLUSIONS
  These results suggest that PKA signaling is pivotal in pigmentation process itself, while the importance of Wnt/β-catenin signaling should be emphasized in the context of development and differentiation.
authors: Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, South Korea.
authors: Kyung-Il
authors: KI
authors: Kim
authors: Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, South Korea.
authors: Do-Sun
authors: DS
authors: Jeong
authors: Department of Dermatology, Gyeongsang National University Changwon Hospital, Changwon, South Korea.
authors: Eui Chang
authors: EC
authors: Jung
authors: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, South Korea; Skin Med Company, Daejeon, South Korea.
authors: Jeung-Hoon
authors: JH
authors: Lee
authors: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, South Korea. Electronic address: cdkimd@cnu.ac.kr.
authors: Chang Deok
authors: CD
authors: Kim
authors: Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, South Korea. Electronic address: yoontj@gnu.ac.kr.
authors: Tae-Jin
authors: TJ
authors: Yoon
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry; D008543:Melanins / Q000737:chemistry; D008544:Melanocytes / Q000166:cytology; D008545:Melanoma / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation; D011494:Protein Kinases / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C115163:CREB1 protein, human; C495270:CTNNB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C492448:ICG 001; D007546:Isoquinolines; D008543:Melanins; D011744:Pyrimidinones; D013449:Sulfonamides; D051153:Wnt Proteins; D051176:beta Catenin; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: ICG-001; Protein kinase A; Wnt/β-catenin signaling