Delta-Tocotrienol Causes Decrease of Melanin Content in Mouse Melanoma Cells

Abstract

We examined the effect of δ-tocotrienol on melanin content in mouse melanoma B16 cells. Melanin content was significantly reduced in cells treated with 50 and 100 µM δ-tocotrienol, but not 10 µM δ-tocotrienol. The activity and amount of tyrosinase also significantly decreased in cells treated with 10, 50, and 100 µM δ-tocotrienol. Furthermore, the mRNA level of tyrosinase as measured using realtime PCR was significantly decreased compared to controls in cells treated with 100 µM δ-tocotrienol, but not 10 or 50 µM δ-tocotrienol. These results indicated that at first δ-tocotrienol caused tyrosinase degradation, and then caused a further decrease in the tyrosinase protein level via both tyrosinase degradation and a decrease in the mRNA level of tyrosinase. We conclude that the decrease of melanin content in the cells by δ-tocotrienol was the result of the decrease of the protein level of tyrosinase (tyrosinase degradation is more important than the decrease of mRNA).

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

“…13) In the present study, the amount of protein in cells treated with 50 mM d-tocotrienol for 48 or 72 h was similar to that in control cells, however, the amount in cells treated with 100 mM d-tocotrienol for 48 h decreased by 60%, as compared with control values. It was reported that a tocotrienol-rich fraction from palm oil, but not alpha-tocopherol, reduced the viability of activated pancreatic stellate cells by setting up a full death program, independent of cell cycle regulation, and activated pancreatic stellate cells died both through apoptosis, as indicated by increased DNA fragmentation and caspase activation, and through autophagy, as denoted by the formation of autophagic vacuoles and LC3-II accumulation.…”

“…We previously reported that tyrosinase degradation is more important than the decrease of mRNA, as cells treated with 50 mM d-tocotrienol for 24 h was caused the reduction of protein level of tyrosinase, but not mRNA level. 13) From these findings, it was suggested that the degradation of melanosome may be caused by the bulk degradation of transient autophagy induced by d-tocotrienol. The results may be caused by the decrease in melanin synthesis-related enzymes.…”

“…We previously reported that the decrease (35%) in the melanin content of mouse melanoma B16 cells treated with 50 mM d-tocotrienol for 24 h was the result of a decrease in the level of tyrosinase. 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).…”

Anti-Melanogenic Activities of Heracleum moellendorffii via ERK1/2-Mediated MITF Downregulation

“…Interestingly, these polyphenols have been partially reported to have both antioxidative and anti-melanogenic effects in acerola [28]. As for the antimelanogenic effects of antioxidants, quercetin was shown to inhibit melanin biosynthesis in B16 cells via a decrease in the protein level of tyrosinase [29]. Plausibly, the inhibitory effects of HmHae on the melanogenesis of melan-a cells are attained through the downregulation of MITF and its upstream tyrosinase, TYRP-1 and TYRP-2, by the polyphenolic components.…”

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

“…17) Use of δ-tocotrienol as a therapeutic or preventive drug for hyperpigmentation or as a component of whitening and/or lightening cosmetics, may result in the release of lysosomes or melanosomes from and a decrease in the cholesterol content of cells as side effects.…”