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

The effect of eight vitamin E analogues (d-α-, dl-α-, d-β-, d-γ-, and d-δ-tocopherols, d-α- and dl-α-tocopheryl acetates) and 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMC) on melanogenesis were compared in mouse B16 melanoma cells. D-β-tocopherol at 250 μg 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-γ-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-β- and d-γ-tocopherols was observed without cytotoxicity up to a concentration of 250 μg ml−1. Weak activity was also observed with d-δ-tocopherol at 8 μg ml−1 and with PMC at 16 μg ml−1, with 19% and 25% inhibition of melanin synthesis, respectively. However, PMC did not directly inhibit tyrosinase, as was observed with d-β-, d-γ-, and d-δ-tocopherols. Analysis by reverse transcription-polymerase chain reaction showed that the mechanism of melanogenesis inhibition by d-β- and d-γ-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-β-tocopherol and d-γ-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.