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.