Pulsed Electromagnetic Field Increases Doxorubicin-induced Mitotic Slippage in MDA-MB-231 Breast Cancer Cells

<h3>Background/Aim:</h3> Pulsed electromagnetic fields (PEMF) can be used to improve the efficacy of chemotherapeutic agents, such as doxorubicin (DOX). DOX induces mitotic slippage, leading to cell death in various cancers including breast cancer. Herein, we investigated whether PEMF exposure enhances DOX-induced mitotic slippage and subsequent cell death in breast cancer cells. <h3>Materials and Methods:</h3> DOX-treated MDA-MB-231 breast cancer cells were stimulated with a 60 min PEMF session three times daily. Cell viability was assessed using the trypan blue exclusion assay. Cell cycle distribution and polyploidy were assessed using flow cytometry, and the morphological features of mitotic slippage were observed microscopically. Western blotting and confocal microscopy were used to evaluate the key molecules involved in G₂/M transition, mitotic transition, and caspase-mediated cell death. <h3>Results:</h3> DOX treatment for three days induced mitotic slippage including cell enlargement, polyploidy, and multinucleation, which was further enhanced by PEMF exposure. DOX treatment also induced CDK1 activation, histone H3 dephosphorylation, and survivin and PLK1 downregulation, which were further increased by PEMF exposure. In addition, CDK1 inhibition reduced mitotic slippage phenotypes and suppressed caspase-2–dependent cell death, resulting in partial restoration of cell viability in the DOX+PEMF group. <h3>Conclusion:</h3> PEMF promotes DOX-induced mitotic slippage and subsequent caspase-2-dependent cell death in MDA-MB-231 cells by modulating cell cycle checkpoint regulators such as CDK1, survivin, and PLK1. These findings suggest that PEMF may serve as a novel adjuvant to potentiate the anticancer efficacy of DOX by increasing DOX-induced mitotic slippage.