Breast Cancer Research and Treatment

, Volume 58, Issue 2, pp 87–97

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

  • Patrick Diel
  • Kai Smolnikar
  • Horst Michna
Article

Abstract

There is increasing evidence that induction of apoptosis by antihormones is an important mechanism in regard to their growth inhibitory action on hormone dependent tumors. In this report we have compared the efficiency of tamoxifen (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 antiestrogens. Application of the pure antiestrogen ZM led to a significantly higher induction of apoptosis compared to the partial agonistic compound Tam. The ability of the two compounds to induce apoptosis correlated with their growth inhibitory action. On the molecular level administration of ZM led to a time dependent steady decrease of BCL‐2 mRNA and protein. Administration of Tam also initially decreased the expression of BCL‐2. In contrast to ZM treatment, BCL‐2 expression increased again after 8 h of incubation with 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 expression may explain the superiority of the pure antiestrogen to induce apoptosis and to inhibit the growth of MCF‐7 cells.

antiestrogens apoptosis BCL‐2 breast cancer MCF‐7 tamoxifen ZM 182780 

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Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Patrick Diel
    • 1
  • Kai Smolnikar
    • 1
  • Horst Michna
    • 1
  1. 1.Department of Morphology and Tumor ResearchDSHS CologneCologneGermany

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