TABLE 3.

Effects of tocotrienol and skin pigmentation.

Studies	Study design	Changes with tocotrienol treatment
Ng et al. (2014)	Cells: B16 melanoma cell line	↑ ERK cascade
	Treatment: δ-tocotrienol or arbutin for 24 h at various concentrations. The cells were stimulated with α-MSH before treatment	↓ Tyrosinase, TYRP-1, TYRP-2, Melanogenesis-related proteins
Makpol et al. (2014)	Cells: A primary culture of melanocytes was exposed to repeated doses of UVA for 6 days	↓ Tyrosinase, melanin synthesis, TYR, TYRP1, TYRP 2 genes
	Treatment: tyrostat, TRF or tocopherol alone or in combination
Michihara et al. (2010)	Cells: B16 cells	↓ Melanin content, Tyrosinase, TRP-1, TRP-2 ( 25 or 50 µM δ-tocotrienol)
	Treatment: 25, 50 or 100 µM δ-tocotrienol for 48 h or 72 h
Yap et al. (2010)	Cells: B16 melanoma cells	↓(Cells) Tyrosinase, melanin content
	Treatment: T3 isomers in a dose-dependent manner for 24 h	↓(Animal) tumor size, pigmentation of solid tumor
	Animal: Nude mice
	Treatment: divided into control untreated group and γ-T3 treated group (100 mg/kg/day). The γ-T3 group were pretreated 1 week before B 16 cells inoculated onto the skin followed by 2-week post-treatment

Abbreviations: ↑ increase, upregulate; ↓ decrease, inhibit or downregulate; ERK, extracellular signal-regulated kinases; TYR, tyrosinase gene; TRP/TYRP1/2, tyrosinase related protein 1/2; UVA, ultraviolet A; γ-T3, gamma-tocotrienol; α-MSH, alpha-melanocyte-stimulating hormone.