The pure antiestrogen ICI 182780 is more effective in the induction of apoptosis and down regulation of BCL-2 than tamoxifen in MCF-7 cells

There is increasing evidence that induction of apoptosis by antihormones is an important mechanism in regard to their growth inhibitory action on horm one dependent tumors. In this report we have compared the efficiency of tam oxifen (Tam) and the pure antiestrogen ICI 182780 (ZM) to induce apoptosis in the estrogen dependent breast cancer cell line MCF-7. Clear evidence for induction of apoptosis could be demonstrated after treatment with both ant iestrogens. Application of the pure antiestrogen ZM led to a significantly higher induction of apoptosis compared to the partial agonistic compound Ta m. The ability of the two compounds to induce apoptosis correlated with the ir growth inhibitory action. On the molecular level administration of ZM le d to a time dependent steady decrease of BCL-2 mRNA and protein. Administra tion of Tam also initially decreased the expression of BCL-2. In contrast t o ZM treatment, BCL-2 expression increased again after 8 h of incubation wi th Tam. After 96 h Tam treated cells expressed BCL-2 levels nearly as high as untreated cells. In general, ZM decreased BCL-2 levels more effectively than Tam. Our results demonstrate that ZM and Tam possess quantitative and qualitative differences in their ability to down regulate BCL-2 expression. The higher ability of the pure antiestrogen to down regulate BCL-2 express ion may explain the superiority of the pure antiestrogen to induce apoptosi s and to inhibit the growth of MCF-7 cells.