Effects of high-isoflavone soy diet vs. casein protein diet and obesity on DMBA-induced mammary tumor development

Abstract

Abstract. Obesity and elevated serum insulin growth factor-1 (IGF-1) level are major risk factors in the development of breast cancer. We investigated the long-term effects of highisoflavone soy intake and obesity on 7,12-dimethylbenz(a) anthracene (DMBA)-induced mammary tumor development and on serum IGF-1 and binding protein (IGFBP-3) levels. Lean and obese female Zucker rats fed casein or highisoflavone soy protein were orally gavaged at age 50 days with DMBA and sacrificed after 147 days. The majority of lean casein-fed rats (69%) developed mammary tumors compared to 50% in lean soy-fed rats (P=0.176). In the obese groups, 76% of soy-fed rats developed mammary tumors compared to 15% of obese casein-fed rats (P<0.001). At age 43 days, IGFBP-3 was increased in the lean soy-fed rats compared to the lean casein-fed rats (P<0.05). At age 99 days, soy-and obese casein-fed rats exhibited increased serum IGF-1 compared to the lean rats and this increase was maintained for the rest of the experiment (P<0.05). Obese rats fed casein exhibited increased IGFBP-3 levels (P<0.001). However, obese rats fed soy exhibited a significant decrease in IGFBP-3 levels compared to the lean soy-fed rats (P<0.001) and a significant decrease in IGFBP-3 levels compared to the obese casein-fed rats (P<0.001). At age 197 days, IGFBP-3 levels were increased in obese casein-and soy-fed rats (P<0.001). The results suggest that female Zucker rats fed casein diets are protected against DMBA-induced mammary tumors, which is not the case for those on high-isoflavone soy diet, and changes in the concentration of serum IGFBP-3 may contribute to the incidence of DMBA-induced mammary tumors.

Dietary phosphatidylcholine promotes breast cancer in the hyperlipidemic E0771 murine model

“…Our results reveal that formulating rodent diets with amino acids in place of casein reduce breast cancer development. The results are consistent with previous findings that suggest an association between higher dietary casein intake and increased risk of cancer [46][47][48][49][50][51][52]. Our study provides further evidence that the tumor promoting effects of casein is due to nutrients contained in casein since supplementing diets with all amino acids that are present in casein as replacement for casein decreases breast tumor development in mice.…”

Dietary soy protein induces hepatic lipogenic enzyme gene expression while suppressing hepatosteatosis in obese female Zucker rats bearing DMBA-initiated mammary tumors

“…We previously reported the growth curves, body weights and mammary tumor data for the animals studied here (Hakkak et al 2011). Obese rats gained significantly more weight than lean rats and at termination of the study, the obese soy-fed rats were significantly heavier than the obese casein-fed rats.…”

“…The semi-purified diet was similar to the AIN-93G diet formulation (Harlan Teklad, Madison, WI) and was prepared with equivalent amounts of dietary protein, either casein (control) or a partially hydrolyzed soy protein isolate with high-isoflavone content [3.24 mg total isoflavones/g protein (1.88 aglycone equivalents/g protein), Lot#M330024462; Solae LLC, St. Louis, MO]. The compositions of both diets are described in Table 1 [and in (Hakkak et al 2011)]. At 50 days of age, all rats, as part of an experiment examining the effects of high-isoflavone soy protein diet and obesity on mammary tumor development (Hakkak et al 2011), received the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA, Sigma Chemical Co., St. Louis, MO), via gavage (65 mg DMBA/kg body weight in sesame oil).…”

“…The compositions of both diets are described in Table 1 [and in (Hakkak et al 2011)]. At 50 days of age, all rats, as part of an experiment examining the effects of high-isoflavone soy protein diet and obesity on mammary tumor development (Hakkak et al 2011), received the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA, Sigma Chemical Co., St. Louis, MO), via gavage (65 mg DMBA/kg body weight in sesame oil). Rats were euthanized at approximately 200 days of age.…”

“…From these, 5-lm liver sections were cut and stained with hematoxylin and eosin. Tumor parameters noted for this study have been recently described (Hakkak et al 2011).…”