The depigmenting effect of ?-tocopheryl ferulate on human melanoma cells

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Abstract
Oral vitamin E (α-tocopherol, α-T) supplementation has been reported to improve facial hyperpigmentation. α-Tocopheryl ferulate (α-TF) is a compound of α-T and ferulic acid connected by an ester bond; ferulic acid is also an antioxidant, and could scavenge free radicals induced by ultraviolet (UV) radiation, and thus maintain the long-lasting antioxidative effect of α-T. Our aim was to see whether α-TF might be useful as a whitening agent and an antioxidant to improve and prevent facial hyperpigmentation following UV exposure. In this study, the inhibitory effect of α-TF on melanogenesis was examined biochemically using human melanoma cells in culture. The results show that α-TF, solubilized in ethanol or in 0.5% lecithin, inhibited melanization significantly, as did α-T at a concentration of 100 μg/mL, without inhibiting cell growth. This phenotypic change was associated with inhibition of tyrosinase and 5,6-dihydroxyindole-2-carboxylic acid polymerase activities, and the degree of inhibition was dose dependent. No significant effect on DOPAchrome tautomerase activity was observed. α-TF did not directly inhibit tyrosinase activity of the large granule fraction extracted from human melanoma cells, and Western blotting revealed that there were no changes in protein content or in molecular size of tyrosinase, tyrosinase-related protein (TRP)-1 or TRP-2. Therefore, the inhibition of tyrosinase activity by α-TF might be due to effects at the post-translational level, and possibly by a secondary molecule activated by α-TF. These results suggest that α-TF is a candidate for an efficient whitening agent which suppresses melanogenesis and inhibits biological reactions induced by reactive oxygen species.