Sensitization to doxorubicin resistance in breast cancer cell lines by tamoxifen and megestrol acetate

Biochemical Pharmacology
L PanasciB Leyland-Jones

Abstract

Acquired drug resistance is a major factor in the failure of doxorubicin-based chemotherapy in breast cancer. We determined the ability of megestrol acetate and/or tamoxifen to reverse doxorubicin drug resistance in a doxorubicin-resistant breast cancer line (the human MCF-7/ADR). The cytotoxicity of doxorubicin, megestrol acetate, and/or tamoxifen was determined in the sensitive and resistant cell lines utilizing the sulphorhodamine B assay. Tamoxifen alone produced an IC50 (concentration resulting in 50% inhibition of control growth) of 10.6 microM, whereas megestrol acetate alone resulted in an IC50 of 48.7 microM in the MCF-7/ADR cell line. The IC50 of doxorubicin in MCF-7/ADR was 1.9 microM. Neither megestrol acetate alone nor tamoxifen alone at 1 or 5 microM altered the IC50 of doxorubicin. However, the combination of tamoxifen (1 or 5 microM) and megestrol acetate (1 or 5 microM) synergistically sensitized MCF-7/ADR cells. Additionally, megestrol acetate and tamoxifen inhibited iodoarylazidoprazosin binding to P-glycoprotein, and, in their presence, there was an increased doxorubicin accumulation in the MCF-7/ADR cells. Furthermore, the combination of tamoxifen and megestrol acetate had much less effect on the cytotoxici...Continue Reading

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Citations

Oct 10, 2012·Endocrine-related Cancer·Francesmary ModugnoSteffi Oesterreich
Oct 5, 2010·Women's Health·T S KristedjaM Cristea
Aug 2, 2015·The International Journal of Biochemistry & Cell Biology·Daniel Gabriel PonsJordi Oliver
Oct 16, 2004·The Journal of Pharmacy and Pharmacology·Valery AlakhovT Alan Hatton
Aug 10, 2007·Phytotherapy Research : PTR·Carina DennyMary Ann Foglio
Mar 28, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·M H LiH S Peng

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