Effect of δ-tocotrienol on melanin content and enzymes for melanin synthesis in mouse melanoma cells.
In the present study, we investigated the dose-dependent effect of delta-tocotrienol long term (48, 72 h) on the melanin content of cells treated with delta-tocotrienol, and whether cells treated with delta-tocotrienol for long a time show cytotoxicity. We also examined whether other enzymes responsible for melanin biosynthesis, tyrosinase-related protein-1 (TRP-1) and -2 (TRP-2), are involved in the decrease in melanin levels. Protein levels in cells treated with 25 or 50 microM delta-tocotrienol for 48 h or 72 h were similar to those in control cells. Melanin content decreased by 44 (25 microM delta-tocotrienol) to 50% (50 microM) at 48 h, and by 14 to 21% at 72 h, compared to control levels. Tyrosinase activity, amounts of tyrosinase and TRP-1 decreased dependent on dose : by 50 (25 microM delta-tocotrienol) to 75% (50 microM), 20 to 45% and 42 to 82% at 48 h, and by 25 to 50%, 75 to 80% and 78 to 77% at 72 h, respectively. Although the amount of TRP-2 increased by 20% on treatment with 25 microM delta-tocotrienol for 48 h, it decreased by 52% on treatment with 50 microM delta-tocotrienol for 48 h. The amount of TRP-2 dose-dependently decreased by 55% and 75% on 72 h by treatment with 25 and 50 microM delta-tocotrienol, respectively. From these findings, delta-tocotrienol at up to 50 microM dose-dependently caused a reduction in melanin content by the decrease of TRP-1 and TRP-2 as well as tyrosinase, and no cytotoxicity.
Michihara
Akihiro
A
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan. mitihara@fupahrm.fukuyama-u.ac.jp
Ogawa
Saki
S
Kamizaki
Yohei
Y
Akasaki
Kenji
K
D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000201:enzymology*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D007370:Interferon Type I; D008543:Melanins; D011257:Pregnancy Proteins; C020947:interferon tau; D014810:Vitamin E; C082097:tocotrienol, delta; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase