title: Docosahexaenoic acid inhibits melanin synthesis in murine melanoma cells in vitro through increasing tyrosinase degradation.
abstract: OBJECTIVE
  To investigate the effects of docosahexaenoic acid (DHA) on melanin synthesis and related regulatory mechanisms.
  
  
  METHODS
  B16F10 mouse melanoma cells were exposed to DHA for 3 d, and melanin content and tyrosinase activity were measured. Western blot analysis was used to analyze the protein levels in DHA-mediated signal transduction pathways.
  
  
  RESULTS
  DHA (1-25 μmol/L) did not affect the viability of B16F10 cells, but decreased α-MSH-induced melanin synthesis in a concentration-dependent manner. DHA concentration-dependently reduced tyrosinase activity in the cells, but did not affect mushroom tyrosinase activity in a cell-free system. Furthermore, DHA treatment significantly reduced tyrosinase level without affecting microphthalmia-associated transcription factor (MITF) in the cells. DHA did not activate ERK and Akt in the cells. Pretreatment with the proteasome inhibitor MG132 (80 nmol/L) abolished DHA-induced tyrosinase reduction.
  
  
  CONCLUSIONS
  DHA inhibits melanogenesis in B16F10 cells in vitro through increasing tyrosinase degradation. The results suggest that DHA may be a potential agent for treatment of hyperpigmentary disorders of skin.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Marie Carmel
authors.initials: MC
authors.lastname: Balcos
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Hyo-soon
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Hye-young
authors.initials: HY
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.affiliation: Department of Dermatology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Kyoungki-do 463-707, Korea.
authors.forename: Kyoung-chan
authors.initials: KC
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Dong-seok
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D012880:Skin Pigmentation / Q000187:drug effects; D013997:Time Factors; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D061988:Proteasome Inhibitors; D004281:Docosahexaenoic Acids; D000521:alpha-MSH; D014442:Monophenol Monooxygenase; D046988:Proteasome Endopeptidase Complex