Abstract 2826: Electromagnetic fields and hyperthermia induce lysosomal permeabilization and death in different cancer cell models: in vitro and in vivo studies

Abstract

Abstract Introduction: Non-ionizing radiations (NIR), e.g. tumor-treating fields, high intensity focused ultrasounds (HIFU) or high frequency microwaves, have potential applications in Oncotherapy. Nevertheless, as today, their efficacy is limited. We investigated whether externally applied magnetic fields and non-ablative hyperthermia affect cancer cell viability and growth. Methods: Under in vitro conditions, human A2058 melanoma, AsPC1 pancreas carcinoma, and MDA-MB-231 breast carcinoma cells were treated with electromagnetic fields (EMFs, using solenoids) and/or hyperthermia (HT, using a thermostated water bath). The effect of both energies was also studied in combination with standard chemotherapy and targeted therapy. An experimental system combining EMFs and HIFU-induced HT was developed and tested in vivo. Results: EMFs (25 μT, 4h) or HT (52ºC, 40 min) quite moderately affect cancer cell viability. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively). Increased lysosomal permeability, release of cathepsins into the cytosol and activation of the mitochondria-dependent cell death are the underlying mechanisms. Cancer cells were completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. In vivo experiments, using pancreatic cancer xenografts growing in nude mice, show that combination of EMFs, HIFU-induced HT and gemcitabine induces a drastic cancer regression (to approx. 3-4% of control values). Conclusion: Non-invasive NIR (EMFs and HIFU-induced HT) can complement current Oncotherapies. This strategy, associated to current chemotherapy or anti-Hsp70-targeted therapy, may facilitate the elimination of tumors that can be previously located using standard imaging techniques (CT scan and NMR). These results may help to overcome the limitations in the use of different NIR in Oncotherapy. Citation Format: Elena Obrador, Ali Jihad-Jebbar, Rosario Salvador-Palmer, Rafael López-Blanch, María Oriol-Caballo, María Paz Moreno-Murciano, Enrique Navarro, Rosa Cibrián, Jose M. Estrela. Electromagnetic fields and hyperthermia induce lysosomal permeabilization and death in different cancer cell models: in vitro and in vivo studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2826.