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.
International Journal of Oncology
McDonald, C.; Muhlbauer, Jillian; Perlmutter, G.; Taparra, Kekoa; and Phelan, Shelley A., "Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity" (2014). Biology Faculty Publications. 78.
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.
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