Normothermic Microwave Irradiation Induces Death of HL-60 Cells through Heat-Independent Apoptosis

Abstract

Microwaves have been used in various cancer therapies to generate heat and increase tumor cell temperature; however, their use is limited by their side-effects in normal cells and the acquisition of heat resistance. We previously developed a microwave irradiation method that kills cultured cancer cells, including a human promyelomonocytic leukemia (HL-60) cell line, by maintaining a cellular temperature of 37 °C during treatment. In the present study, we investigated the mechanisms underlying HL-60 cell death during this treatment. The microwave-irradiated HL-60 cells appear to undergo caspase-independent apoptosis, whereby DNA fragmentation was induced by mitochondrial dysfunction-related expression of apoptosis-inducing factor (AIF). Caspase-dependent apoptosis was also interrupted by the loss of apoptotic protease-activating factor 1 (Apaf-1) and caspase 9. Moreover, these cells did not exhibit a heat-stress response, as shown by the lack of heat shock protein 70 (HSP70) upregulation. Alternatively, in HL-60 cells heated at 42.5 °C, HSP70 expression was upregulated and a pathway resembling death receptor-induced apoptosis was activated while mitochondrial function was maintained. Collectively, these results suggest that the cell death pathway activated by our 37 °C microwave irradiation method differs from that induced during other heating methods and support the use of normothermic microwave irradiation in clinical cancer treatments.

Microwave hyperthermia promotes caspase‑3-dependent apoptosis and induces G2/M checkpoint arrest via the ATM pathway in non‑small cell lung cancer cells

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Microwave hyperthermia enhances the sensitivity of lung cancer cells to gemcitabine through reactive oxygen species‑induced autophagic death

“…reactions, easy clinical implementation and effectiveness in improving the results of traditional radiochemotherapy, has been widely used as an adjuvant cancer treatment. A large number of clinical studies have confirmed that MWHT can improve the prognosis of patients with cancer, including hepatic, breast, bladder and lung cancer (7)(8)(9)(10)(11)(12)(13). Indeed, the ability of MWHT to enhance the anticancer effects of chemotherapy is well known.…”

Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers

“…Induction of apoptosis in the tissues is in agreement with another study where microwave treatment was shown to induce caspase-dependent apoptosis in a leukaemic cell line. 38 Apoptosis was sustained over at least 72 h and was also observed at sites distal to the treatment site, but at a lower level than that observed at proximal sites. Autophagy markers LC3B and p62 were upregulated upon heat shock in both SiHa (data not shown) and NIKS16 tissues.…”