Reduction of Mevalonate Pyrophosphate Decarboxylase in Mouse Melanoma Cells Treated with δ-Tocotrienol Is Not Associated with Reduction of Cholesterol Content or Release of Lysosomes and Melanosomes

Abstract

We previously reported that a decrease in the melanin content of mouse melanoma cells (B16 cells) treated with δ-tocotrienol was the result of a decrease in the level of tyrosinase activity and protein. Use of δ-tocotrienol as a whitening agent, may therefore have side effects. In the present study, we examined whether δ-tocotrienol caused side effects (the release of lysosomes from and a decrease in the cholesterol content of cells). We also examined the release of melanosomes (lysosome-related organella). Neither of lysosomes nor melanosomes were released from cells treated with δ-tocotrienol, since β-glucuronidase (melanosomal and lysosomal enzyme) activity, melanin content (melanosomal marker), and tyrosinase (melanosomal enzyme) activity did not increase in the cell culture medium. Although mevalonate pyrophosphate decarboxylase (MPD; an enzyme of cholesterol biosynthesis) was significantly reduced in the cells treated with δ-tocotrienol, cholesterol content was not. Thus, δ-tocotrienol might be useful as a therapeutic or preventive drug for hyperpigmentation and as a component of whitening and/or lightening cosmetics not causing severe side effect (reduction of cholesterol content and release of lysosomes/melanosomes), although δ-tocotrienol cause a decrease of MPD.

Effect of Delta-Tocotrienol on Melanin Content and Enzymes for Melanin Synthesis in Mouse Melanoma Cells

“…13) d-Tocotrienol might also be useful as a therapeutic or preventive drug for hyperpigmentation and as a component of whitening and/or lightening cosmetics not causing severe side effect (reduction of cholesterol content and release of lysosomes/melanosomes), although 50 mM dtocotrienol for 24 h caused a decrease in the level of mevalonate pyrophosphate decarboxylases, an enzyme involved in cholesterol biosynthesis. 14) Kamei et al reported that d-tocopherol has cytotoxicity, although it shows antimelanogenic activity at a low concentration long term (72 h). 15) Although in number and position of methyl groups on the chromanol ring, of d-tocotrienol is similar to d-tocopherol, d-tocotrienol possesses a farnesyl instead of a saturated phytyl side chain.…”