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

I. Obiorah, S. Sengupta, P. Fan, V. C. Jordan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1488-1496
Number of pages9
JournalBritish Journal of Cancer
Volume110
Issue number6
DOIs
StatePublished - Mar 18 2014
Externally publishedYes

Bibliographical note

Funding Information:
This work (VCJ) was supported by the Department of Defense Breast Program under Award number W81XWH-06-1-0590. Center of Excellence; the Susan G Komen for the Cure Foundation under Award number SAC100009 and the Lombardi Comprehensive Cancer 1095 Center Support Grant (CCSG) Core Grant NIH P30 CA051008. The views and opinions of the author(s) do not reflect those of the United States Army or the Department of Defense.

Keywords

  • 4-hydroxy tamoxifen
  • chemotherapy
  • E2
  • endoplasmic reticulum stress
  • oestrogen receptor
  • paclitaxel
  • RT-PCR
  • TNF

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