Soy processing influences growth of estrogen-dependent breast cancer tumors

Abstract

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(R)), 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(R), 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(R), 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.

Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF‐7 human breast cancer xenografts

“…However, unlike FS diet, the long-term administration of SP diet stimulated the growth of orthotopic MCF-7 xenografts in ovariectomized mice, which concur with the previous studies of Allred and co-workers 9,22 although in this work the tumors grew slower. In our study, however, the energy density was higher than in previous studies 9,22 as high-fat diets (20% corn oil) were fed to mice, while the other studies 9,22 used low fat diet (7% corn oil).…”

“…In our study, however, the energy density was higher than in previous studies 9,22 as high-fat diets (20% corn oil) were fed to mice, while the other studies 9,22 used low fat diet (7% corn oil). The use of high-fat led to lower consumption of SP diet and hence phytoestrogen in our study than in the other studies, 9,22 which may in part explain the observed slower rate of tumor growth.…”

“…In many in vitro studies with MCF-7 cells, soy isoflavones have been shown to increase the proliferation of the cells in concentration dependent manner 6,36,37 and to inhibit apoptosis, 38 which agrees with the findings in MCF-7 xenograft model in vivo showing increased tumor growth via increased cell proliferation after consumption of isoflavone-rich diets. 9,11,22 The mammalian lignan metabolites of plant lignans in FS, enterodiol and especially enterolactone, have also been shown to increase the MCF-7 cell proliferation. 39,40 However, these in vitro findings of mammalian lignans are not in agreement with the findings in vivo as no hormone responsive mammary tumor growth stimulating effect of FS 12,13,20 or enterolactone 11,15 has been demonstrated.…”

Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF‐7 xenografts in ovariectomized athymic nude mice

“…19,35,36 GEN increased the proliferation of the MCF-7 cells in vitro in part through modulation of the IGF-I signalling pathway. 37 Furthermore, GEN is known to bind preferentially to ERb.…”

Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status

“…Isoflavones are also known to act independent of the ERs through their antiproliferative, antiangiogenic, antioxidative and anti-inflammatory properties (Setchell et al, 2002). In addition to isoflavones, soybeans also contain other bioactive components that may be associated with chemoprevention (for example, protease inhibitors, phenolic acids, lignans, phytosterols and saponins) (Allred et al, 2004). Furthermore, several studies have reported possible synergistic effects of these components (Omoni and Aluko, 2005;Kim et al, 2008).…”