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

Abstract

BackgroundDietary 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.MethodsFour 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.ResultsThere 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.ConclusionsTaken 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.

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12‐dimethylbenz[a]anthracene‐induced mammary carcinogenesis in female rat offspring

“…The increased cell proliferation in the mammary gland of the Se‐DEF female offspring could represent another mechanism underlying paternal programming of breast cancer risk. Se has been shown to exert cell cycle regulatory effects in breast cancer cells and breast tumor‐bearing animals . In maternal intervention studies Se deficiency altered the expression of cell cycle control genes in the offspring's colonic tissue .…”

“…Se has been shown to exert cell cycle regulatory effects in breast cancer cells and breast tumor-bearing animals. 40,41 In maternal intervention studies Se deficiency altered the expression of cell cycle control genes in the offspring's colonic tissue. 21 On the other hand, the observation of decreased apoptosis in both Se-DEF and Se-SUP female offspring mammary glands suggests that this cellular process is not directly linked to increased breast cancer risk in the former group.…”

Micronutrients and Breast Cancer Progression: A Systematic Review

“…The analyzed preclinical studies showed an inverse relationship between circulating levels of Se and vascular epithelial growth factor (VEGF) [78]. Se supplementation seemed to inhibit tumor progression in preclinical studies and cell cultures [79]. A decrease in Se levels appears to be widespread in cancer progression, but there is no evidence of its benefits as an adjuvant in tumor progression.…”

Paternal nutrition and cancer programming: the influence of selenium deficiency or supplementation on the susceptibility of female offspring to chemically-induced mammary carcinogenesis

“…The increased cell proliferation in the mammary gland of the Se-DEF female offspring could represent another mechanism underlying paternal programming of breast cancer risk. Se has been shown to exert cell cycle regulatory effects in breast cancer cells and breast tumor bearing animals [40,41]. In maternal intervention studies…”

“…As most of selenoproteins exerts antioxidant activity, it was proposed that increased Se status could protect DNA against oxidative damage (Moghadaszadeh & Beggs 2006) Concerning breast cancer, interest was increased because of initial studies showing that Se status in blood and nails was lower in breast cancer patients than in healthy subjects (Männistö et al, 2000;Rejali et al, 2007) and some epidemiological studies showed a correlation between Se status and breast cancer risk . (Ip, 1981;Thompson et al, 1982;Thompson et al, 1989) and mice supplementation with organic/inorganic Se or selenized milk casein decreased growth of intramammary tumors (Chen et al, 2013;Warrington et al, 2013).…”