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

Br J Cancer. 2014 Mar 18;110(6):1488-96. doi: 10.1038/bjc.2014.50. Epub 2014 Feb 18.


Background: Oestrogen (E2) induces apoptosis in long-term E2-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 E2 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: E2-induced apoptosis is a delayed process, whereas paclitaxel immediately inhibits the growth and induces death of MCF7:5C cells. The cellular commitment for E2-triggered apoptosis occur after 24 h. Activation of the intrinsic pathway was observed by 36 h of E2 treatment with subsequent induction of the extrinsic apoptotic pathway by 48 h. Paclitaxel exclusively activated extramitochondrial apoptotic genes and caused rapid G2/M blockade by 12 h of treatment. By contrast, E2 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 E2-induced apoptosis can be reversed after 24 h treatment.

Conclusions: These data indicate that E2-induced apoptosis involves a novel, multidynamic process that is distinctly different from that of a classic cytotoxic chemotherapeutic drug used in breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Estrogens / pharmacology*
  • Female
  • Humans
  • MCF-7 Cells
  • Paclitaxel / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • Estrogens
  • Paclitaxel