Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.

The Associations of Percent Body Fat with Dietary Intake, Plasma Lipids, Lipoprotein(a), and PAI-1 in Middle Aged Korean Adults / 대한지역사회영양학회지

This study was designed to investigate the associations of the percent body fat dietary intake, plasma lipoprotein profile, lipoprotein(a), and plasminogen activator inhibitor-1(PAI-1) concentrations of 1982 Korean subjects(men : 1000 and women : 982) between the ages of 40 and 59 years. The dietary assessment consisted of twenty-four hour dietary records and food frequency questionnaires. The subjects were identified into one of the five rating groups of % body fat : lean, underweight, normal, overweight and obese groups. The biochemical assessment included measurements of plasma total cholesterol(TC), HDL-cholesterol(HDL-C), LDL-cholesterol(LDL-C), triglyceride(TG), lipoprotin(a)(Lp(a)), and PAI-1. With respect to the ratio of percent energy intake of carbohydrate : protein : fat of the normal group of the women was 62% : 17% : 20%, respectively. Women apparently had a higher intake of carbohydrates than men(52% : 17 : 20%) did. There was a linear relationship between energy intake and % body fat in both mean and women(with the exception of the underweight group of women). The relationship of % body fat of men to the protein and fat intake was higher than that of the carbohydrate intake. Of the men in the study, intakes of energy, protein and alcohol were positively correlated to % body fat. In women, energy, carbohydrate and protein intake were positively correlated to % body fat, however, the fat, cholesterol and alcohol intake did not show any correlation to the % body fat in women. This study showed that % body fat was positively correlated with plasma TC, LDL-C, PAI-1 levels, and TG, but the % body fat was negatively correlated with plasma HDL-C level in both men and women. These results indicated that the high energy intake of obese or overweight subjects might contribute to several of the biochemical indices fo coronary heart disease(CHD) risk. In conclusion, increased energy intake is associated with overweight or obesity in middle aged Korean people. There was no relationship between % energy intake of fat and % body fat in the study, in middle-aged Korean men and women. The plasma lipid profile and PAI-1 level thought to be the risk factors of CHD were positively associated with percent body fat in middle aged Korean people.