Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells

Elena Obrador
ORCID logo ,
Ali Jihad-Jebbar
,
Rosario Salvador-Palmer
ORCID logo ,
Rafael López-Blanch
,
María Oriol-Caballo
,
María Paz Moreno-Murciano
,
Enrique Navarro
ORCID logo ,
Rosa Cibrian
ORCID logo ,
José M. Estrela
*
Version 1 : Received: 6 May 2023 / Approved: 8 May 2023 / Online: 8 May 2023 (08:53:59 CEST)

A peer-reviewed article of this Preprint also exists.

Obrador, E.; Jihad-Jebbar, A.; Salvador-Palmer, R.; López-Blanch, R.; Oriol-Caballo, M.; Moreno-Murciano, M.P.; Navarro, E.A.; Cibrian, R.; Estrela, J.M. Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells. Cancers 2023, 15, 3413. Obrador, E.; Jihad-Jebbar, A.; Salvador-Palmer, R.; López-Blanch, R.; Oriol-Caballo, M.; Moreno-Murciano, M.P.; Navarro, E.A.; Cibrian, R.; Estrela, J.M. Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells. Cancers 2023, 15, 3413.

Abstract

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. 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 mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

Keywords

Non-ionizing radiations; Electromagnetic fields; Hyperthermia; Cancer therapy; Cancer cell death

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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