Soy extract inhibits mammary adenocarcinoma growth in a syngeneic mouse model

• Published in: Cancer letters 2003-03, Vol.192 (2), p.133-143
• Main Authors: Hewitt, Amy L., Singletary, Keith W.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Animals; Biological and medical sciences; Body Weight - drug effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell cycle; Cell Cycle Proteins - metabolism; Cell Division - drug effects; Cell growth; Cell Line; Cell Movement - drug effects; Cyclin-dependent kinases; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Genistein - pharmacology; Genistein - therapeutic use; Glycine max - chemistry; Isoflavones - pharmacology; Isoflavones - therapeutic use; Kinases; Mammary adenocarcinoma; Medical sciences; Mice; Neoplasm Invasiveness; p21 waf1/cip1; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Soy
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(02)00712-7

The effects of the soybean isoflavone genistein and a commercially-available isoflavone-containing soy extract on the growth of F3II mouse mammary adenocarcinoma cells were investigated. Female Balb/c mice injected (s.c.) with F3II cells and fed diets supplemented with 0.6% soy extract (containing genistein at 750 ppm) exhibited a significant 90% reduction in tumor weight compared to controls, whereas female mice fed diets supplemented with 750 ppm genistein alone exhibited a significant 40% reduction in tumor weight compared to controls. Tumor samples from animals fed the 0.6% soy extract, but not from those animals fed the 750 ppm genistein diet alone, exhibited significantly higher protein levels of the cyclin-dependent kinase inhibitor p21 waf1/cip1 compared to controls. Neither of the two experimental diets altered tumor estrogen receptor-α or progesterone receptor protein levels. In vitro, genistein significantly inhibited F3II cell proliferation (IC 50 ∼2–3 μM) and caused a G2/M block in cell cycle progression at concentrations as low as 5 μM. This genistein-induced G2/M arrest in vitro was associated with a significant increase in the protein expression of phosphorylated p34 cdc2 and of cyclin B1. These results indicate that genistein is an inhibitor of F3II mouse mammary adenocarcinoma cell growth in vivo and in vitro, in part due to its effect on specific cell cycle regulatory proteins. In addition, genistein fed to mice as part of the soy extract resulted in a greater magnitude of inhibition of mouse mammary adenocarcinoma tumor growth, compared to tumor growth of animals fed an equivalent amount of genistein alone. This suggests that genistein along with other constituent(s) in the soy extract may also contribute to suppression of F3II tumor growth.