Inhibition of growth and stimulation of apoptosis by beta-sitosterol treatment of MDA-MB-231 human breast cancer cells in culture

Epidemiological and experimental studies have suggested a protective role o f phytosterols (PS) in the development of some types of cancer such as colo n and prostate cancer. No work has been reported on the role of PS in the d evelopment of breast cancer, the second leading cancer in woman. The presen t study was designed to examine the effect of the two most common dietary P S, beta-sitosterol (SIT) and campesterol, as compared to cholesterol, the m ain sterol in the Western diet, on growth, apoptosis and cytotoxicity of MD A-MB-231 human breast cancer cells in culture. In addition, we investigated the possible role of protein phosphatase 2A (PP2A), an enzyme that has bee n shown to regulate growth and apoptosis in tumor parameters studied. Breas t cancer cell growth was found to be inhibited by 66% after 3 days and 80% after 5 days with 16 mu M SIT. Both campesterol and cholesterol sustained t umor growth at levels comparable to that of the vehicle control. None of th e sterols tested at this level (16 mu M) induced cytotoxicity as measured b y lactic dehydrogenase release. SIT supplementation for 3 days at 16 mu M r esulted in a 6-fold increase in apoptosis in cells when compared to cholest erol treated cells. SIT treatment was found to have no effect on the level and content of tumor cell PP2A. It is concluded that SIT, by a still unknow n mechanism, may offer protection from breast cancer by inhibiting growth a nd stimulating apoptosis.