Evaluation of the cancer chemopreventive efficacy of rice bran in genetic mouse models of breast, prostate and intestinal carcinogenesis

Abstract

Brown rice is a staple dietary constituent in Asia, whereas rice consumed in the Western world is generally white, obtained from brown rice by removal of the bran. We tested the hypothesis that rice bran interferes with development of tumours in TAg, TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) or Apc(Min) mice, genetic models of mammary, prostate and intestinal carcinogenesis, respectively. Mice received rice bran (30%) in AIN-93G diet throughout their post-weaning lifespan. In TAg and TRAMP mice, rice bran did not affect carcinoma development. In TRAMP or wild-type C57Bl6/J mice, dietary rice bran increased kidney weight by 18 and 20%, respectively. Consumption of rice bran reduced numbers of intestinal adenomas in Apc(Min) mice by 51% (P<0.01), compared to mice on control diet. In parallel, dietary rice bran decreased intestinal haemorrhage in these mice, as reflected by increased haematocrit. At 10% in the diet, rice bran did not significantly retard Apc(Min) adenoma development. Likewise, low-fibre rice bran (30% in the diet) did not affect intestinal carcinogenesis, suggesting that the fibrous constituents of the bran mediate chemopreventive efficacy. The results suggest that rice bran might be beneficially evaluated as a putative chemopreventive intervention in humans with intestinal polyps.

Figure 1

Effect of rice bran on whole body weight of TAg mice (A), TRAMP mice and their wild-type (C57Bl/6J) counterparts (B) or Apc^Min mice (C). Mice received control diet or diet fortified with rice bran at 30%. Results are the mean±s.d. of 12–16 mice. For details of animal experimentation, see Materials and methods.

Figure 2

Lack of effect of rice bran on mammary carcinogenesis in TAg mice as reflected by survival (A), tumour volume (B), tumour multiplicity (C) and tumour weight (D). Mice received control diet (open bars) or 30% rice bran in the diet (closed bars) from week 3 after weaning for their lifetime. Animals were killed when tumour diameter exceeded 17 mm. Volume, multiplicity and weights of tumours were determined at the termination of the experiment. Results are the mean±s.d. (n=12 for controls and 15 for intervention group). For details of experimental design and assessment of TAg tumour development see Materials and methods.

Figure 3

Effect of rice bran on weight of the following tissues in TRAMP mice (A, C–E) or C57Bl/6J (wild-type) mice (B–E): prostate carcinoma plus seminal vesicles (A), normal prostate plus seminal vesicles (B), liver (C), lung (D) and kidney (E). Mice received control diet (open bars) or diet fortified with 30% rice bran (closed bars) from weaning for their lifetime. Tissue weight was determined at the termination of the experiment. Results are the mean±s.d. of 12–16 mice. Stars indicate that liver weight in TRAMP mice was significantly lower than that in wild-type mice (^*P<0.02, ^**P<0.005), and crosses indicate that kidney weights in mice on rice bran were significantly higher than those in mice on control diet (⁺⁺P<0.002). For details of experimental design and assessment of tissue weight, see Materials and Methods.

Figure 4

Effect of 30% dietary rice bran on adenoma number in the small intestine (A) or colon (B) and on haematocrit (C) in Apc^Min mice. Mice received control diet (open bars) or diet fortified with 30% rice bran (closed bars) from week 3 after weaning for their lifetime. Results are the mean±s.d., n=15. Stars indicate that value is significantly different from control (^*P<0.05, ^**P<0.01, ^***P<0.001). For details of experimental design and assessment of adenoma number, see Materials and Methods.

Figure 5

Effect of dietary 30% dietary rice bran on adenoma multiplicity in the proximal (‘prox’), middle and distal sections of the small intestine (A), and on total multiplicity of small (<1 mm diameter), medium-sized (1–3 mm) or large (>3 mm) adenomas (B) in Apc^Min mice. Mice received control diet (open bars) or diet containing 30% rice bran (closed bars) from week 3 after weaning for their lifetime. Results, which are presented as number of adenomas per mouse as related to distribution (A) or size (B), are the mean±s.d. (n=15). Stars indicate that values are significantly different from controls (^*P<0.05, ^**P<0.01, ^***P<0.005). For details of experimental design and assessment of adenoma number, see Materials and Methods.

Figure 6

Lack of effect of 10% dietary rice bran (closed bars) or 30% dietary low-fibre rice bran (crossed bars) on adenoma number in the small intestine (A) or colon (B) and on haematocrit (C) in Apc^Min mice. Mice received control diet (open bars) or diet fortified with 10% rice bran (closed bars) or 30% low-fibre rice bran (crossed bars) from week 3 after weaning for their lifetime. Results are the mean±s.d., n=16–17. For details of experimental design and assessment of adenoma number, see Materials and Methods.