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. 2010 Feb;13(1):70-6.
doi: 10.1089/jmf.2009.0042.

Dietary zinc and prostate cancer in the TRAMP mouse model

Ananda S Prasad  1 , Hasan Mukhtar, Frances W J Beck, Vaqar M Adhami, Imtiaz A Siddiqui, Maria Din, Bilal B Hafeez, Omer Kucuk
Affiliations

Dietary zinc and prostate cancer in the TRAMP mouse model

Ananda S Prasad et al. J Med Food. 2010 Feb.

Abstract

Circumstantial evidence indicates that zinc may have an important role in the prostate. Total zinc levels in the prostate are 10 times higher than in other soft tissues. Zinc concentrations in prostate epithethial cancer cells are decreased significantly. Zinc supplementation for prevention and treatment of prostate cancer in humans has yielded controversial results. No studies have been reported in animal models to show the effect of zinc supplementation on prevention of prostate cancer, thus far. In this study, we have examined the effect of zinc supplementation on development of prostate cancer in a TRAMP mouse model. Results from our study indicate that dietary zinc plays an important role in prostate carcinogenesis. Tumor weights were significantly higher when the dietary zinc intake was either deficient or high in comparison to normal zinc intake level, suggesting that an optimal dietary zinc intake may play a protective role against prostate cancer. Further, our studies also showed decreased insulin-like growth factor (IGF)-1 and IGF-1/IGF binding protein-3 ratio in normal zinc-supplemented animals, suggesting that zinc may modulate IGF-1 metabolism in relation to carcinogenesis. We conclude that optimal prostate zinc concentration has a protective role against cancer.

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Figures

FIG. 1.
FIG. 1.
Average daily consumption of food for mice fed zinc-deficient diet (control), diet containing 30 ppm zinc (normal), and diet containing 150 ppm zinc (high level). Data are mean ± SD values (n = 6 mice per group). There were no significant differences among the three groups.
FIG. 2.
FIG. 2.
Average body weight gain over the course of 20 weeks for mice fed three experimental Zn diets. Data are mean ± SD values for data collected at 12, 16, and 20 weeks (n = 6 mice per group). There were no significant differences among the three groups.
FIG. 3.
FIG. 3.
Average prostate weights at 22 weeks for mice fed zinc-deficient diet (control), diet containing 30 ppm zinc (normal), and diet containing 150 ppm zinc (high). Data are mean ± SD values (n = 6 mice per group). Prostate tumor weights were significantly lower in mice given 30 ppm zinc diet compared to the zinc-deficient and zinc-excess groups (P < .05). Prostate weights were as follows: Zn-deficient, 680 ± 280 mg; zinc normal, 490 ± 110 mg; and high zinc, 800 ± 330 mg.
FIG. 4.
FIG. 4.
Serum IGF-1 levels determined at the end of 22 weeks in mice fed zinc-deficient diet (control), diet containing 30 ppm zinc (normal), and diet containing 150 ppm zinc (high). Data are mean ± SD values (n = 6 mice per group). Serum IGF-1 levels were significantly lower in mice fed 30 ppm Zn compared to Zn-deficient mice (P < .01). The IGF-1 level was higher in mice fed 150 ppm zinc (high) compared to Zn-deficient mice (P < .05). Serum IGF-1 levels were as follows: Zn-deficient, 140 ± 40 ng/mL; zinc normal, 75 ± 15 ng/mL; and high zinc, 225 ± 60 ng/mL.
FIG. 5.
FIG. 5.
Serum IGFBP-3 levels determined at the end of 22 weeks in mice fed zinc-deficient diet (control), diet containing 30 ppm zinc (normal), and diet containing 150 ppm zinc (high). Data are mean ± SD values (n = 6 mice per group). No significant differences were observed among the three groups. Serum IGFBP-3 levels were as follows: Zn-deficient, 13 ± 3 ng/mL; zinc normal, 12 ± 3 ng/mL; and high zinc, 10 ± 4 ng/mL.
FIG. 6.
FIG. 6.
Ratio of serum IGF-1 to IGFBP-3 levels, determined at the end of 22 weeks in mice fed Zn-deficient diet (control), diet containing 30 ppm zinc (normal), and diet containing 150 ppm zinc (high). Data are mean ± SD values for the ratio of serum IGF-1 to IGFBP-3 (n = 6 mice per group). The ratio was significantly decreased in mice fed 30 ppm zinc in comparison to the other two groups.
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