Antitumor effects of dietary black and brown rice brans in tumor-bearing mice: relationship to composition

Mol Nutr Food Res. 2013 Mar;57(3):390-400. doi: 10.1002/mnfr.201200515. Epub 2012 Dec 23.

Abstract

Scope: Feeding a diet supplemented with 10% (w/w) black and brown rice brans inhibited growth of transplanted tumors in mice.

Methods and results: Black and brown rice brans from Oryza sativa LK1-3-6-12-1 and Chuchung cultivars each contained 21 compounds characterized by GC/MS. Mice fed diets with added rice brans for 2 weeks were intracutaneously inoculated with CT-26 mouse cancer cells and fed the same diet for two additional weeks. Tumor mass was 35 and 19% lower in the black and brown bran-fed groups, respectively. Tumor inhibition was associated with increases in cytolytic activity of splenic natural killer (NK) cells; partial restoration of nitric oxide production and phagocytosis in peritoneal macrophages; increases in released tumor necrosis factor-α, IL-1β, and IL-6 from macrophages; increases in infiltration of leukocyte into the tumor; and reduction in angiogenesis inside the tumor. Proangiogenic biomarkers vascular endothelial growth factor, cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) were also reduced in mRNA and protein expression. ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX. Reduced COX-2 and 5-LOX expression downregulated vascular endothelial growth factor and inhibited neoangiogenesis inside the tumors.

Conclusion: Induction of NK activity and macrophages and inhibition of angiogenesis seem to contribute to tumor regression.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase / metabolism
  • Body Weight / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Diet
  • Dietary Supplements
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Killer Cells, Natural / drug effects
  • Leukocytes / drug effects
  • Leukocytes / pathology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / diet therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Nitric Oxide / metabolism
  • Oryza / chemistry*
  • Phagocytosis / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Arachidonate 5-Lipoxygenase
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2