The prevention of breast cancer through dietary modification is an active area of clinical and epidemiological research. It has been proposed that dietary supplementation of vitamin E may reduce a woman's risk of developing breast cancer. However, the exact mechanism remains unknown. alpha-Tocopherol is the most biologically active form of vitamin E. We investigated the effect of vitamin E (alpha-tocopherol) on breast cancer cell growth. A dose-dependent inhibition of cell proliferation was found in estrogen receptor (ER)-positive cells showing a potent suppression of growth at 100 microM vitamin E in MCF-7 (53%) and T47D (75%) cells. Vitamin E reduced significantly the response of both cell lines to estrogen (10 nM), and cell proliferation was decreased in MCF-7 and T47D cells by 69% and 84%, respectively. No growth inhibition was observed when cells were grown in the absence of estrogen. Vitamin E altered and decreased the growth inhibition induced by tamoxifen (10 microM) in MCF-7 (33%) and T47D (54%) cells. In addition, the immunostaining of ER of MCF-7 cells was reduced by 30% in the presence of vitamin E, suggesting an effect of vitamin E on the expression of ER. This provides evidence that vitamin E may inhibit ER-positive cell growth by altering the cellular response to estrogen.