Lack of stimulatory activity of a phytoestrogen-containing soy extract on the growth of breast cancer tumors in mice.
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 17beta-estradiol, it displayed antiestrogenic activity. The expression of other genes involved in tumor progression and angiogenesis, such as Thrombospondin 1, Transforming Growth Factor beta2 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.
Gallo
Daniela
D
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Lgo A. Gemelli, 8-00168, Rome, Italy. d.gallo@rm.unicatt.it
Ferlini
Cristiano
C
Fabrizi
Manuela
M
Prislei
Silvia
S
Scambia
Giovanni
G
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D030262:Soybean Proteins / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D048789:Phytoestrogens; D010936:Plant Extracts; D030262:Soybean Proteins