Soy extract inhibits mammary adenocarcinoma growth in a syngeneic mouse model
Amy L Hewitt1, Keith W Singletary
1Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61801, USA.
Abstract:
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-alpha or progesterone receptor protein levels. In vitro, genistein significantly inhibited F3II cell proliferation (IC(50) approximately 2-3 microM) and caused a G2/M block in cell cycle progression at concentrations as low as 5 microM. 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.
Insights
Soy isoflavones, particularly genistein, inhibit mammary tumor growth in mice. A soy extract containing genistein showed greater tumor reduction than genistein alone, suggesting synergistic effects.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Soy isoflavones, like genistein, are plant compounds with potential anti-cancer properties.
- Mammary adenocarcinoma is a common form of breast cancer in mice, often used to study cancer development and treatment.
Purpose of the Study:
- To investigate the effects of genistein and a soy extract on F3II mouse mammary adenocarcinoma cell growth.
- To determine the impact of these compounds on cell cycle regulation and specific protein levels in tumor tissues.
Main Methods:
- In vivo studies using Balb/c mice injected with F3II cells and fed diets supplemented with soy extract or genistein.
- In vitro studies assessing genistein's effect on F3II cell proliferation and cell cycle progression.
- Analysis of protein levels for cyclin-dependent kinase inhibitor p21(waf1/cip1), estrogen receptor-alpha, and progesterone receptor.
Main Results:
- Soy extract significantly reduced tumor weight by 90%, while genistein alone reduced it by 40%.
- Soy extract increased p21(waf1/cip1) protein levels, unlike genistein alone.
- Genistein inhibited F3II cell proliferation in vitro and induced a G2/M cell cycle block, increasing phosphorylated p34(cdc2) and cyclin B1 levels.
Conclusions:
- Genistein inhibits F3II mouse mammary adenocarcinoma cell growth in vivo and in vitro by affecting cell cycle proteins.
- Soy extract containing genistein demonstrated a greater inhibitory effect on tumor growth than genistein alone, suggesting other soy constituents contribute to tumor suppression.
