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Title:   Author  item
                                            KIM, SUNG PHIL - Ajou University Of Koreaitem
                                            KANG, MI YOUNG - Kyungpook National Universityitem
                                            NAM, SEOK HYUN - Ajou University Of Koreaitem
                                            Friedman, Mendel
  Submitted to: Molecular Nutrition and Food Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/24/2012
                                    Publication  Date: 3/30/2012
                                    Citation: Kim, S., Kang, M., Nam, S., Friedman, M. 2012. Dietary rice component ¿-Oryzanol inhibits tumor growth in tumor-bearing Mice. Molecular Nutrition and Food Research. DOI 10.1002/mnfr.201200057.Interpretive Summary: Rice bran from whole grain brown rice and rice bran oil are rich sources of a large number of bioactive secondary metabolites.  In previous collaborative studies with Korean scientists we found that aqueous/ethanol bran extracts from several black rice cultivars exhibited potent antioxidative, antimutagenic, anti-inflammatory, and anticarcinogenic effects in chemical and cell assays and that a rice hull smoke extract exhibited anti-inflammatory and antimicrobial effects against Salmonella in mice. The main objective of the present study was to investigate the ability of the bran ingredients '-oryzanol, Ricetrienol®, ferulic and phytic acids, and of rice bran to reduce tumor size and associated biomarkers in mice intracutaneously transplanted on their backs with CT-26 colon cancer cells. We found that compared to the control diet without the rice bran ingredient, oral administration for two weeks of '-oryzanol to mice with induced tumors significantly reduced tumor size in a dose-dependent manner by up to 44%. Further studies showed that the inhibition of tumor growth was accompanied with changes in several ex vivo and in vivo biomarkers associated with normal and tumor cells. These considerations suggest that '-oryzanol may have therapeutic potential against human cancers. It would be of interest to find out whether the '-oryzanol content of brans from different rice varieties correlates with anticarcinogenic and antimicrobial activities.
                                Technical Abstract: 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, '-oryzanol, Ricetrienol®, ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet for 2 additional weeks. Tumor mass was significantly lower in the '-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 pro-inflammatory cytokines tumor necrosis factor-a, IL-1ß, 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 down-regulated VEGF and inhibited neo-angiogenesis inside the tumors.  Conclusions: Induction of natural killer spleen cell activity, activation of macrophages, and inhibition of angiogenesis seem to contribute to the inhibitory mechanism of tumor regression.


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