Comparative study on the induction of cytostasis and apoptosis by ICI 182,780 and tamoxifen in an estrogen receptor-negative ovarian cancer cell line
Abstract
We have compared the effects of a broad range of clinically relevant concentrations (0.1 to 10 microM) of the steroidal pure anti-estrogen ICI 182,780 and the non-steroidal partial anti-estrogen tamoxifen (TAM) on cell proliferation and induction of apoptosis in the estrogen receptor (ER)-negative ovarian carcinoma cell line A2780. Cell proliferation was assessed by evaluating the number of viable cells, changes in cell-cycle distribution and cell replication rate; while apoptosis induction was assessed by examining nuclear morphological changes associated with apoptotic death and DNA cleavage into 300 and 50 kbp units (large DNA fragmentation) and into 180 bp units (internucleosomal DNA fragmentation). We provide evidence that 0.1 to 10 microM ICI 182,780 and TAM significantly inhibit the growth of A2780 cells in a dose-dependent fashion. Cytokinetic analysis revealed that only 10 microM TAM caused a significant blockade in G1 and a diminished replication rate. Conversely, we show that 0.1 to 10 microM ICI 182,780 and TAM induce apoptosis in a dose-dependent fashion. The earliest recognizable apoptotic change induced by treating the cells with these 2 drugs was DNA cleavage into 300 and 50 kbp units. This started to be visible...Continue Reading
References
Tamoxifen. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use.
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis