Pulsed Electromagnetic Field Potentiates Daunorubicin-induced Post-slippage Cell Death in MDA-MB-231 Cells

Abstract

Objectives: Anthracycline remains a cornerstone of breast cancer chemotherapy.Although pulsed electromagnetic field (PEMF) exposure enhances doxorubicin efficacy, whether this effect extends to other anthracyclines is unclear.This study investigated whether PEMF potentiates daunorubicin (Dn) cytotoxicity in a breast cancer cell line and elucidated its molecular mechanisms.Methods: MDA-MB-231 cells were treated with 30 nM Dn and exposed to 70 Hz PEMF (2.5 mT) for one hour, three times daily.Cell viability was measured using trypan blue exclusion.Cell cycle progression was analyzed by flow cytometry.Apoptotic and G2/M regulatory proteins were evaluated via western blotting.Results: PEMF significantly enhanced Dn-induced cytotoxicity, accompanied by increased levels of cleaved poly(adenosine diphosphate-ribose) polymerase and cleaved caspase-2.Flow cytometry demonstrated that PEMF accelerated progression from G2/M arrest to mitotic slippage, increasing polyploidy.Furthermore, PEMF promoted aberrant G2/M transition by enhancing CDK1 activation and reducing proteins that sustain G2/M arrest, while amplifying early DNA damage signaling.Conclusion: These findings indicate that PEMF enhances the anticancer efficacy of Dn by accelerating DNA damage accumulation, promoting aberrant G2/M transition, enhancing mitotic slippage, and triggering caspase-2-dependent cell death.