Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity

  • Authors:
    • C. McDonald
    • J. Muhlbauer
    • G. Perlmutter
    • K. Taparra
    • S. A. Phelan
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  • Published online on: April 24, 2014     https://doi.org/10.3892/ijo.2014.2398
  • Pages: 219-226
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Abstract

Peroxiredoxin (Prdx) proteins are thiol-specific antioxidants that protect cells from oxidative stress in many normal and disease states. There are six Prdx proteins expressed in mammals, each with a characteristic tissue expression, subcellular distribution and substrate specificity. Recent studies have revealed elevated Prdx levels in many cancers, suggesting a protective role for these proteins in cancer cell survival. The present study is the first to investigate the function of all six Prdx proteins in the MCF-7 breast cancer cell line. We show that these cells have both higher resistance to doxorubicin‑induced toxicity and significantly elevated Prdx levels, compared to the non‑cancer MCF-10A cells. Using transient siRNA transfections, we show that Prdx3 suppression leads to decreased MCF-7 cell survival in the absence of doxorubicin. We further demonstrate that individual suppression of four of six of the Prdx proteins leads to increased doxorubicin-induced toxicity by apoptosis. Finally, we show that clonal selection of a doxorubicin-resistant MCF-7 subline by 2-week culture in 0.1 µM doxorubicin resulted in a marked elevation in the expression of several Prdx proteins. Together, these data reveal a protective function for peroxiredoxins in MCF-7 cell survival, and suggest that Prdx overexpression in breast cancer may play a role in doxorubicin-resistance in these, and possibly other, breast cancer cells. This study is the first to investigate the function of the entire Prdx family in a breast cancer cell line.
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July-2014
Volume 45 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
McDonald C, Muhlbauer J, Perlmutter G, Taparra K and Phelan SA: Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity. Int J Oncol 45: 219-226, 2014.
APA
McDonald, C., Muhlbauer, J., Perlmutter, G., Taparra, K., & Phelan, S.A. (2014). Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity. International Journal of Oncology, 45, 219-226. https://doi.org/10.3892/ijo.2014.2398
MLA
McDonald, C., Muhlbauer, J., Perlmutter, G., Taparra, K., Phelan, S. A."Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity". International Journal of Oncology 45.1 (2014): 219-226.
Chicago
McDonald, C., Muhlbauer, J., Perlmutter, G., Taparra, K., Phelan, S. A."Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity". International Journal of Oncology 45, no. 1 (2014): 219-226. https://doi.org/10.3892/ijo.2014.2398