title: Comparable down-regulation of TYR, TYRP1 and TYRP2 genes and inhibition of melanogenesis by tyrostat, tocotrienol-rich fraction and tocopherol in human skin melanocytes improves skin pigmentation.
abstract: OBJECTIVE
  Antioxidant has been recognized to inhibit UV-induced melanogenesis. This study aimed to elucidate the molecular mechanism of tyrostat, tocopherol and tocotrienol-rich fraction in inhibiting melanogenesis in human skin melanocytes.
  
  
  METHODS
  Primary culture of melanocytes was exposed to repeated doses of 0.6 J/cm2 UVA for 6 days and treated with tyrostat, tocotrienol-rich fraction or tocopherol alone or in combination.
  
  
  RESULTS
  UVA irradiation increased melanin content and tyrosinase activity and up-regulated TYR, TYRP1 and TYRP2 genes. Treatment with tyrostat, tocotrienol-rich fraction or tocopherol decreased melanin content and down-regulated TYR, TYRP1 and TYRP2 genes with decreased tyrosinase activity. Combined treatment exerted better effects as compared to treatment with single compound in decreasing the melanin content and down-regulating TYR, TYRP1 and TYRP2 genes. These findings indicated that tyrostat, tocotrienol-rich fraction and tocopherol inhibit melanogenesis by modulating the expression of genes involved in the regulation of melanin synthesis and inhibiting tyrosinase activity.
  
  
  CONCLUSIONS
  Tyrostat, tocopherol and tocotrienol-rich fraction possessed anti-melanogenic properties and might be useful in improving skin pigmentation caused by UVA exposure.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: S
authors.initials: S
authors.lastname: Makpol
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: F A
authors.initials: FA
authors.lastname: Jam
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: N A
authors.initials: NA
authors.lastname: Rahim
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: S C
authors.initials: SC
authors.lastname: Khor
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia, and 2R&D Plantation and Agri-Business Division, Sime Darby Research Sdn Bhd, 42960 Carey Island, Selangor, Malaysia.
authors.forename: Z
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Y A M
authors.initials: YA
authors.lastname: Yusof
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Wan Ngah
mesh_terms: D000970:Antineoplastic Agents; D000975:Antioxidants / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects*; D024505:Tocopherols / Q000494:pharmacology*; D024508:Tocotrienols / Q000494:pharmacology*; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D008543:Melanins; D008562:Membrane Glycoproteins; D024508:Tocotrienols; D014810:Vitamin E; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D024505:Tocopherols