Delayed triggering of oestrogen induced apoptosis that contrasts with rapid paclitaxel-induced breast cancer cell death

Background: Oestrogen (E ₂ ) induces apoptosis in long-term E ₂ -deprived MCF7 cells (MCF7:5C). Taxanes have been used extensively in the treatment of early and advanced breast cancer. We have interrogated the sequence of events that involve the apoptotic signalling pathway induced by E ₂ in comparison with paclitaxel. Methods: DNA quantification and cell cycle analysis were used to assess proliferation of cancer cells. Apoptosis was evaluated using annexin V and DNA staining methods. Regulation of apoptotic genes was determined by performing PCR-based arrays and RT-PCR. Results: E ₂ -induced apoptosis is a delayed process, whereas paclitaxel immediately inhibits the growth and induces death of MCF7:5C cells. The cellular commitment for E ₂ -triggered apoptosis occur after 24 h. Activation of the intrinsic pathway was observed by 36 h of E ₂ treatment with subsequent induction of the extrinsic apoptotic pathway by 48 h. Paclitaxel exclusively activated extramitochodrial apoptotic genes and caused rapid G2/M blockade by 12 h of treatment. By contrast, E ₂ causes an initial proliferation with elevated S phase of cell cycles followed by apoptosis of the MCF7:5C cells. Most importantly, we are the first to document that E ₂ -induced apoptosis can be reversed after 24 h treatment. Conclusions: These data indicate that E ₂ -induced apoptosis involves a novel, multidynamic process that is distinctly different from that of a classic cytotoxic chemotherapeutic drug used in breast cancer.