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

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.

The functional role of peroxiredoxin 3 in reactive oxygen species, apoptosis, and chemoresistance of cancer cells

“…Since most of chemotherapy for cancers is through increase in ROS level and apoptotic induction of cancer cells (Srinivas et al 2004;Alexandre et al 2006;Singh et al 2007;Brown et al 2010), some researchers have suggested PRX3 to be a potential target for cancer therapy on the basis of above fact Song et al 2011). Although the overlapping peroxidatic activities of PRXs contributed to drug resistance of cancer cells (Kalinina et al 2012), PRX3 played an indispensable role in apoptotic regulation (Chua et al 2010;Li et al 2013b;Whitaker et al 2013;Wang et al 2014;McDonald et al 2014). Therefore, we have reason to look forward to the desired effects by suppressing the expression of PRX3.…”

“…Simultaneous over-expression of PRX3 and other PRX genes (Table 1) indicates that PRXs work synergistically to protect cancer cells against oxidative stress (Shen and Nathan 2002;McDonald et al 2014). Notably, PRX3 was prominently up-regulated in nearly all the cancers except MM, in which the PRX3 positivity (36 % of all detected cases) was less than that of PRX1 (69 %), PRX2 (75 %), PRX5 (67 %), and PRX6 (83 %) (Kinnula et al 2002).…”

Knockdown of PRDX2 sensitizes colon cancer cells to 5-FU by suppressing the PI3K/AKT signaling pathway

“…PRDX proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity [16]. PRDX6 overexpression attenuated cisplatin-induced apoptosis in human ovarian cancer cells [17].…”

Redox Regulating Enzymes and Connected MicroRNA Regulators Have Prognostic Value in Classical Hodgkin Lymphomas

“…There is increasing evidence from in vitro studies that PRDX II may block especially doxorubicin-mediated cell death [36, 37]. PRDX I and II overexpression have also been connected to poorer prognostic factors in several carcinomas [36, 38–40].…”