Dietary rice bran component γ-oryzanol inhibits tumor growth in tumor-bearing mice

Scope: We investigated the effects of rice bran and components on tumor growth in mice. Methods and results: Mice fed standard diets supplemented with rice bran, gamma-oryzanol, Ricetrienol (R), ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet for two additional weeks. Tumor mass was significantly lower in the gamma-oryzanol and less so in the phytic acid group. Tumor inhibition was associated with the following biomarkers: increases in cytolytic activity of splenic natural killer (NK) cells; partial restoration of nitric oxide production and phagocytosis in peritoneal macrophages increases in released the pro-inflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 from macrophages; and reductions in the number of blood vessels inside the tumor. Pro-angiogenic biomarkers vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and 5-lipoxygenase-5 (5-LOX) were also significantly reduced in mRNA and protein expression by tumor genes. ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX up to 30%. Reduced COX-2 and 5-LOX expression downregulated VEGF and inhibited neoangiogenesis inside the tumors. Conclusion: Induction of NK activity, activation of macrophages, and inhibition of angiogenesis seem to contribute to the inhibitory mechanism of tumor regression by gamma-oryzanol.