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

McDonald,C.; Muhlbauer,J.; Perlmutter,G.; Taparra,K.; Phelan,S. A.

doi:10.3892/ijo.2014.2398

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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Affiliations: Fairfield University, Fairfield, CT 06824, USA
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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