Soy processing influences growth of estrogen-dependent breast cancer tumors

• Published in: Carcinogenesis (New York) 2004-09, Vol.25 (9), p.1649-1657
• Main Authors: Allred, Clinton D., Allred, Kimberly F., Ju, Young H., Goeppinger, Tracy S., Doerge, Daniel R., Helferich, William G.
• Format: Article
• Language: English
• Subjects: 5-bromo-2′-deoxyuridine; Animals; Apoptosis; Aromatase - metabolism; Biological and medical sciences; BrdU; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinogenesis, carcinogens and anticarcinogens; Cell Cycle - drug effects; Cyclin D1 - metabolism; Diet; estrogen receptors; Estrogens - pharmacology; Female; Food Handling; Genistein; Humans; Medical sciences; Mice; Mice, Nude; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Ovariectomy; progesterone receptor; Proteins - metabolism; Receptors, Progesterone - metabolism; Soy Foods; Trefoil Factor-1; Tumor Cells, Cultured; Tumor Suppressor Proteins; Tumors
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/bgh178

Soy-based products consumed in Asian countries are minimally processed whereas in the USA many of the soy foods and soy ingredients are highly processed. Soy foods contain complex mixtures of bioactive compounds, which may interact with one another. The objective of this study was to evaluate the ability of various soy products containing genistin, the glycoside form of genistein, to affect growth of MCF-7 cells transplanted into ovariectomized athymic mice. Products investigated included soy flour, two crude extracts of soy (soy molasses and Novasoy®), a mixture of isoflavones and genistin in pure form. Each of the soy flour-processed products was added to the diet to provide equivalent amounts of genistein aglycone equivalents (750 p.p.m.). Tumors in the negative control animals regressed throughout the study while the tumors in the soy flour-fed animals remained basically the same size (neither grew nor regressed). In animals consuming soy molasses, Novasoy®, mixed isoflavones or genistin alone, tumor growth was stimulated when compared with animals consuming a control diet devoid of soy. These same dietary treatments resulted in increased cellular proliferation. Changes in mRNA expression of gene targets (estrogen responsiveness, cell cycle progression, apoptosis and aromatase activity) in tumors induced by the different diets were evaluated. The relative expression of pS2, progesterone receptor and cyclin D1 was increased in animals consuming the Novasoy®, mixed isoflavones and genistin. Bcl2 mRNA expression was low in most of the dietary treatment groups compared with positive (estradiol implant) controls. Aromatase expression was not affected in any of the treatment groups. The degree of soy flour processing affects the estrogenicity of products containing a constant amount of genistein. Collectively, these findings suggest that for postmenopausal women with estrogen-dependent breast cancer, the consumption of foods containing soy flour is more advisable than consuming isoflavones in more purified forms.