Pulsed Electromagnetic Field Promotes Doxorubicin-induced Apoptosis by Increasing Caspase-2 Activation in MDA-MB-231...

Doxorubicin (DOX) is an effective chemotherapeutic drug for breast cancer. Pulsed electromagnetic field (PEMF) stimulation improves the efficacy of chemotherapeutic agents. However, whether PEMF stimulation modulates DOX-induced caspase-2-dependent apoptosis remains unclear. Thus, this study investigated the effect of PEMF exposure on DOX-induced apoptosis in MDA-MB-231 breast cancer cells.

MDA-MB-231 cells were seeded, and the growth medium was replaced with DOX-containing medium and was either unstimulated or stimulated with 1 h PEMF sessions thrice a day at 4-h intervals for up to 72 h. Cell viability was measured using the trypan blue dye exclusion assay, and cell cycles were analyzed using flow cytometry. The molecular mechanisms underlying apoptosis were confirmed by western blotting.

PEMF stimulation further reduced the viability of DOX-treated MDA-MB-231 cells. Moreover, it increased the percentage of cells in the sub-G₁ phase and cleavage of PARP in DOX-treated MDA-MB-231 cells. PEMF enhanced the DOX-induced activation of caspase-3/7/9 and truncation of Bid. Additionally, PEMF exposure further enhanced the DOX-induced activation of caspase-2 in MDA-MB-231 cells. Caspase-2 inhibition not only suppressed the PEMF-mediated increase in Bid truncation and cleavage of caspase-3/7/9 and PARP, but also significantly restored the PEMF-enhanced reduction of the viability of DOX-treated MDA-MB-231 cells.

PEMF stimulation can further increase DOX-induced caspase-2 activation, which consequently potentiates Bid truncation and the subsequent activation of the intrinsic apoptotic pathway, further reducing the viability of DOX-treated MDA-MB-231 breast cancer cells.