Comparison of the inhibitory effects of vitamin E analogues on melanogenesis in mouse B16 melanoma cells

The effect of eight vitamin E analogues (d-alpha-, dl-alpha-, d-beta-, d-gamma-, and d-delta-tocopherols, d-alpha- and dl-alpha-tocopheryl acetates) and 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMC) on melanogenesis were compared in mouse B16 melanoma cells. D-beta-tocopherol at 250 mug ml(-1) inhibited not only 28% of melanin synthesis in B16 cells, but also 34% of the Tyrosinase activity, a very important cascade enzyme involved in the synthesis of melanin in melanoma cells. D-gamma-tocopherol also strongly inhibited up to 39% of melanin synthesis and 45% of the Tyrosinase enzyme activity at the same concentration. The inhibitory activity of both d-beta- and d-gamma-tocopherols was observed without cytotoxicity up to a concentration of 250 mug ml(-1). Weak activity was also observed with d-delta-tocopherol at 8 mug ml(-1) and with PMC at 16 mug ml(-1), with 19% and 25% inhibition of melanin synthesis, respectively. However, PMC did not directly inhibit Tyrosinase, as was observed with d-beta-, d-gamma-, and d-delta-tocopherols. Analysis by reverse transcription-polymerase chain reaction showed that the mechanism of melanogenesis inhibition by d-beta- and d-gamma-tocopherols in cells might be attributed to reduced expression of Tyrosinase and Tyrosinase related protein-2 mRNA in addition to direct inhibition of the Tyrosinase. These findings suggest that both d-beta-tocopherol and d-gamma-tocopherol might be useful as effective ingredients in whitening cosmetics with lower skin toxicity to prevent or improve skin pigmentation such as skin spots and freckles caused by UV exposure.