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¹ Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
² Department of Oncology, Catholic University of the Sacred Heart, 86100 Campobasso, Italy

(Requests for offprints should be addressed to G Scambia who is now at Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo A Gemelli, 8-00168 Rome, Italy; Email: giovanni.scambia{at}rm.unicatt.it)

The study reported here was designed to determine whether a phytoestrogen-containing soy extract (SSE) could negate/overwhelm the inhibitory effects of ICI 182 780 on the growth of estrogen-sustained human breast cancer xenografts (MCF-7), in ovariectomized athymic mice. As expected, estradiol-supplemented tumors did not grow over the study period in ICI 182 780-treated females; concomitant administration of 50 mg/kg per day SSE slightly potentiated the inhibitory activity of the drug, while at 100 mg/kg per day, SSE partially negated ICI 182 780 activity. In keeping with these in vivo outcomes, we observed that the level of cyclin D1 (and progesterone receptor) in MCF-7 xenografts was considerably reduced by ICI 182 780, an effect enhanced by concomitant treatment with 50 SSE, but reduced by the higher dosage (i.e. 100 mg/kg per day). Thrombospondin-1 (TSP-1) and kallikrein 6 (KLK6) levels were also reduced following ICI 182 780, although to a lesser degree; again, combined anti-estrogen and SSE produced a dose-dependent regulation in TSP-1 and KLK6 tumor level, with a further reduction in the mRNA gene expression at 50 SSE (compared with ICI 182 780) and a partial reversion of the drug-induced down-regulation at 100 mg/kg per day. No modulation was detected in the serum concentration of IGF-1 (a potent mitogen for estrogen receptor-positive breast cancer cell lines) either upon treatment with ICI 182 780 or concomitant administration of the anti-estrogen with SSE. In conclusion, results from this study raise concerns about the consumption of isoflavone supplements in conjunction with ICI 182 780 therapy, in postmenopausal women with estrogen-dependent breast cancer.

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				D. Gallo, G. F. Zannoni, I. De Stefano, M. Mosca, C. Ferlini, E. Mantuano, and G. Scambia Soy Phytochemicals Decrease Nonsmall Cell Lung Cancer Growth In Female Athymic Mice J. Nutr., July 1, 2008; 138(7): 1360 - 1364. [Abstract] [Full Text] [PDF]