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Open Access Highly Accessed Research article

Selenized milk casein in the diet of BALB/c nude mice reduces growth of intramammary MCF-7 tumors

Jenny M Warrington1, Julie JM Kim1, Priska Stahel1, Scott RL Cieslar1, Roger A Moorehead2, Brenda L Coomber2, Milena Corredig3 and John P Cant1*

Author Affiliations

1 Centre for Nutrition Modelling, Department of Animal and Poultry Science, University of Guelph, Guelph, ON N1G 2W1, Canada

2 Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada

3 Department of Food Science, University of Guelph, Guelph, ON N1G 2W1, Canada

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BMC Cancer 2013, 13:492  doi:10.1186/1471-2407-13-492

Published: 23 October 2013

Abstract

Background

Dietary selenium has the potential to reduce growth of mammary tumors. Increasing the Se content of cows’ milk proteins is a potentially effective means to increase Se intake in humans. We investigate the effects of selenized milk protein on human mammary tumor progression in immunodeficient BALB/c nude mice.

Methods

Four isonitrogenous diets with selenium levels of 0.16, 0.51, 0.85 and 1.15 ppm were formulated by mixing low- and high-selenium milk casein isolates with a rodent premix. MCF-7 cells were inoculated into the mammary fat pad of female BALB/c nude mice implanted with slow-release 17 β-estradiol pellets. Mice with palpable tumors were randomly assigned to one of the four diets for 10 weeks, during which time weekly tumor caliper measurements were conducted. Individual growth curves were fit with the Gompertz equation. Apoptotic cells and Bcl-2, Bax, and Cyclin D1 protein levels in tumors were determined.

Results

There was a linear decrease in mean tumor volume at 70 days with increasing Se intake (P < 0.05), where final tumor volume decreased 35% between 0.16 and 1.15 ppm Se. There was a linear decrease in mean predicted tumor volume at 56, 63 and 70 days, and the number of tumors with a final volume above 500 mm3, with increasing Se intake (P < 0.05). This tumor volume effect was associated with a decrease in the proportion of tumors with a maximum growth rate above 0.03 day-1. The predicted maximum volume of tumors (Vmax) and the number of tumors with a large Vmax, were not affected by Se-casein. Final tumor mass, Bcl-2, Bax, and Cyclin D1 protein levels in tumors were not significantly affected by Se-casein. There was a significantly higher number of apoptotic cells in high-Se tumors as compared to low-Se tumors.

Conclusions

Taken together, these results suggest that turnover of cells in the tumor, but not its nutrient supply, were affected by dairy Se. We have shown that 1.1 ppm dietary Se from selenized casein can effectively reduce tumor progression in an MCF-7 xenograft breast cancer model. These results show promise for selenized milk protein as an effective supplement during chemotherapy.

Keywords:
Selenium; Casein; Mammary tumor; MCF-7 cells