Isoform-specific expression of peroxiredoxins in human cancer cell lines with various radioresistance

To investigate the role of peroxiredoxin isoforms (Prdx) in the radioresistance of cancer cells, the expression of Prdx1-6, DNA repair genes, and apoptosis regulators was studied in human cancer cell lines with varying radiosensitivities (A549, Caco-2, and MCF-7) after exposure to ionizing radiation. A correlation was found between high constitutive Prdx1-6 expression levels and increased radioresistance. Predominantly cytosolic isoforms Prdx2 and Prdx6 demonstrated pronounced induction after irradiation, indicating their critical role in protecting against radiation-induced oxidative stress. Most radiosensitive A549 cells exhibited the lowest baseline Prdx expression and the most pronounced transcriptional changes after irradiation, whereas MCF-7 and Caco-2 cells had higher constitutive expression and a weaker response to radiation. Mitochondrial Prdx3 and Prdx5, as well as ER-localized Prdx4, exhibited relatively stable expression. A549 cells demonstrated the highest induction of DNA repair genes, which may indicate more severe DNA damage. In contrast, MCF-7 cells were characterized by high basal expression of repair genes and elevated γH2AX levels before irradiation, which may reflect their "readiness" for repair and explain their higher radioresistance. Furthermore, radioresistant MCF-7 cells had increased expression of anti-apoptotic genes (BCL2, MCL1, BIRC5), suppressing the mitochondrial apoptotic pathway. Meanwhile, A549 cells showed higher induction of pro-apoptotic genes (PUMA, NOXA, BAK1) and activation of caspase-3, which correlates with their increased radiosensitivity. Therefore, peroxiredoxins protect cells from radiation exposure, either by being constitutively expressed or by being highly inducible in response to radiation, and promote cell survival after irradiation. This makes them attractive targets for overcoming cancer cell radioresistance.