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

• Published in: British journal of cancer 2014-03, Vol.110 (6), p.1488-1496
• Main Authors: Obiorah, I, Sengupta, S, Fan, P, Jordan, V C
• Format: Article
• Language: English
• Subjects: 631/67/1059/99; 631/67/1347; 631/80/82/23; Annexin V; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer Research; Cell cycle; Cell death; Cell Division - drug effects; Cell proliferation; Cytotoxicity; Deoxyribonucleic acid; DNA; Drug Resistance; Epidemiology; Estrogens; Estrogens - pharmacology; Female; Gene regulation; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; MCF-7 Cells; Medical sciences; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Paclitaxel; Paclitaxel - pharmacology; Polymerase chain reaction; S phase; Signal transduction; Translational Therapeutics; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.50

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.