Carcinogenesis Advance Access originally published online on January 7, 2006
Carcinogenesis 2006 27(7):1404-1409; doi:10.1093/carcin/bgi338
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Lack of stimulatory activity of a Phytoestrogen-containing soy extract on the growth of breast cancer tumors in mice
1 Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Lgo A. Gemelli, 8-00168, Rome, Italy and 2 Department of Oncology, Catholic University of the Sacred Heart, Campobasso, Italy
* To whom correspondence should be addressed. Tel/Fax: 06/35508736; E-mail: d.gallo{at}rm.unicatt.it
The present study was designed to investigate the effects of a phytoestrogens-containing soy extract (SOYSELECT®, SSE) on the growth of estrogen-dependent (MCF-7) and estrogen-unresponsive (MDA-MB-231) human breast cancer xenografts in athymic mice. Results obtained provided evidence that MCF-7 tumors did not grow over the treatment period (5 weeks) in ovariectomized females receiving 50 or 100 mg/kg/day SSE (oral route); administration of SSE also did not affect the estradiol-sustained growth of MCF-7 tumors in mice. Similarly, no effects on tumor growth were observed in SSE-treated mice bearing MDA-MB-231 xenografts. Data from pS2, progesterone receptor and cyclin D1 mRNA expression in tumors showed that, although SSE was able to induce a moderate estrogenic effect in MCF-7 cells, it did not increase cellular proliferation and tumor growth, in our experimental conditions. Besides, when used in association with 17ß-estradiol, it displayed antiestrogenic activity. The expression of other genes involved in tumor progression and angiogenesis, such as Thrombospondin 1, Trasforming Growth Factor ß2 and Kallikrein 6 was also evaluated in tumor samples, results showing a decrease in mRNA expression upon SSE treatment. The effect of SSE on angiogenesis in vivo was also evaluated in the Matrigel plug assay; results obtained showed a striking anti-angiogenic activity in mice receiving 100 mg/kg/day SSE, thereby confirming that this extract may interfere with angiogenesis. Collectively, these experimental data suggest that SSE could be not harmful for women with a history of or at high risk for breast cancer, at least for short treatment periods; however, further studies are needed to thoroughly characterize the activity profile of the extract in this specific setting of patients.
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