Document Type

Article

Article Version

Publisher's PDF

Publication Date

2014

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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Copyright 2014 Spandidos Publications

The final publisher PDF has been archived here with permission from the copyright holder.

Publication Title

International Journal of Oncology

Published Citation

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(1), 219-226. https://doi.org/10.3892/ijo.2014.2398.

DOI

10.3892/ijo.2014.2398

Peer Reviewed

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