Ionomycin enhances radiosensitivity in breast cancer through reactive oxygen species generation and mitochondrial...

The frequent resistance of breast cancer to radiotherapy and systemic therapies has resulted in suboptimal outcomes with traditional treatment regimens. Therefore, there is an urgent need to develop more effective methods of treating breast cancer. This study concentrated on measuring the effectiveness of a combination of anti-cancer agent, ionomycin and radiotherapy on breast cancer cells. The combination of ionomycin and radiotherapy resulted in inhibition of the proliferation of breast cancer cells in vitro experiments, which was indicated by cell counting kit-8 and colony formation experiments. Ionomycin and radiotherapy caused Ca 2+ overload in mitochondrial cancer cells, opening the mitochondrial permeability transition pore, inducing reactive oxygen species generation, and increasing DNA double-strand breaks. The reduction in cell viability induced by ionomycin combined with radiotherapy was significantly reversed by N-acetyl-L-cysteine (a reactive oxygen species scavenger) and cyclosporine A (mitochondrial permeability transition pore channel inhibitor). The combination therapy extended the opening of the mitochondrial permeability transition pore in breast cancer cells, causing mitochondrial dysfunction. The prolonged opening of the mitochondrial permeability transition pore has been observed to raise the levels of cytochrome c and the levels of cleaved caspase-3 protein, which eventually resulted in an escalation in the rate of apoptosis. The treatment also decreased the migration and invasion of the breast cancer cells in this combination treatment. This research indicates that ionomycin may function as an effective radiosensitizer, therefore enhancing the efficacy of radiotherapy in the treatment of breast cancer.