title: Stimulation of melanogenesis by scoparone in B16 melanoma cells.
abstract: OBJECTIVE
  The effect of coumarin derivatives on melanogenesis was investigated in B16 murine melanoma cells.
  
  
  METHODS
  Melanin content and tyrosinase activity were analyzed spectrophotometrically. The expression of tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were measured either by reverse transcription-polymerase chain reaction (RT-PCR) or Western blot.
  
  
  RESULTS
  Among the coumarin derivatives studied, scoparone (6,7- dimethoxycoumarin) was the most potent; the 6- or 7-methoxy group was found to be essential for the stimulation of melanogenesis. The melanin content was greatly increased by scoparone in a dose-dependent manner; there was no cytotoxicity at the effective concentrations. Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone. H-89, an inhibitor of protein kinase A (PKA), completely inhibited the scoparone-induced increase of melanogenesis and the tyrosinase protein.
  
  
  CONCLUSIONS
  These results suggest that scoparone-induced stimulation of melanogenesis is likely to occur at the transcriptional level of melanogenesis-related enzymes through PKA signaling.
authors.affiliation: Department of Biochemistry, Dental School, Chonbuk National University, Jeonju 561-756, Korea.
authors.forename: Jeong-yeh
authors.initials: JY
authors.lastname: Yang
authors.forename: Jeung-hyun
authors.initials: JH
authors.lastname: Koo
authors.forename: Young-gil
authors.initials: YG
authors.lastname: Song
authors.forename: Kang-beom
authors.initials: KB
authors.lastname: Kwon
authors.forename: Ju-hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee-sook
authors.initials: HS
authors.lastname: Sohn
authors.forename: Byung-hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Eun-chung
authors.initials: EC
authors.lastname: Jhee
authors.forename: Jin-woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D003374:Coumarins; D007546:Isoquinolines; D008543:Melanins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013449:Sulfonamides; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C018145:scoparone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide