Selenoneine suppresses melanin synthesis by inhibiting tyrosinase in murine B16 melanoma cells and 3D-cultured human melanocytes
The novel organic selenium compound, selenoneine, is found in the blood of tuna and has metal-binding activity. In this report, selenoneine displays tyrosinase inhibitory activity. When murine B16 melanoma cells were cultured in the presence of 1.0 μM selenoneine, the melanin content in the cells was reduced to 46.5% compared with the cell-induced melanin synthesis, and cellular tyrosinase activity was suppressed. In 3D-cultured human melanocytes, melanin accumulation was also decreased, to 39.7% and 23.0% by 1.0 and 5.0 μM selenoneine, respectively, compared with the control cells. Both cellular and purified enzyme assays showed that selenoneine inhibited tyrosinase activity against the substrate, l-3,4-dihydroxyphenylalanine (l-DOPA). An in silico docking simulation study supported a molecular mechanism in which selenoneine chelates copper ions in the active center of tyrosinase and prevents the reaction between tyrosinase and l-DOPA. These findings suggest that selenoneine has a novel biological function by inhibiting tyrosinase via copper chelation.
KeywordsSelenium l-DOPA DOPA quinone Copper Pigmentation
This work was supported by grants from the National Research Institute of Fisheries Science.
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