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Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells
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, developing more efficient heat nanomediators t...
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Published in: | Cancers 2023-06, Vol.15 (13), p.3413 |
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creator | Obrador, Elena Jihad-Jebbar, Ali Salvador-Palmer, Rosario López-Blanch, Rafael Oriol-Caballo, María Moreno-Murciano, María Paz Navarro, Enrique A Cibrian, Rosa Estrela, José M |
description | 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, developing more efficient heat nanomediators that may exhibit high specific absorption rates is still 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 µT, 4 h) or HT (52 °C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approximately 16%, 50%, and 21% of control 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 by 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 a combination of EMFs, HIFU-induced HT, standard chemotherapy, and a lysosomal permeabilizer induces a complete cancer regression. |
doi_str_mv | 10.3390/cancers15133413 |
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In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, developing more efficient heat nanomediators that may exhibit high specific absorption rates is still 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 µT, 4 h) or HT (52 °C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approximately 16%, 50%, and 21% of control 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 by combining EMFs, HT, and standard chemotherapy or EMFs, HT, and anti-Hsp70-targeted therapy. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c443t-44f49cccb231c4983b5c135285de294ae322e5559f77f2d253d2580873c7b67e3</cites><orcidid>0000-0003-3201-7467 ; 0000-0002-5934-5543 ; 0000-0002-0784-6776 ; 0009-0008-6246-0869 ; 0000-0001-8365-0233</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2836340267/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2836340267?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37444524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Obrador, Elena</creatorcontrib><creatorcontrib>Jihad-Jebbar, Ali</creatorcontrib><creatorcontrib>Salvador-Palmer, Rosario</creatorcontrib><creatorcontrib>López-Blanch, Rafael</creatorcontrib><creatorcontrib>Oriol-Caballo, María</creatorcontrib><creatorcontrib>Moreno-Murciano, María Paz</creatorcontrib><creatorcontrib>Navarro, Enrique A</creatorcontrib><creatorcontrib>Cibrian, Rosa</creatorcontrib><creatorcontrib>Estrela, José M</creatorcontrib><title>Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>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, developing more efficient heat nanomediators that may exhibit high specific absorption rates is still 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 µT, 4 h) or HT (52 °C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approximately 16%, 50%, and 21% of control 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 by combining EMFs, HT, and standard chemotherapy or EMFs, HT, and anti-Hsp70-targeted therapy. 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Jihad-Jebbar, Ali ; Salvador-Palmer, Rosario ; López-Blanch, Rafael ; Oriol-Caballo, María ; Moreno-Murciano, María Paz ; Navarro, Enrique A ; Cibrian, Rosa ; Estrela, José M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-44f49cccb231c4983b5c135285de294ae322e5559f77f2d253d2580873c7b67e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Apoptosis</topic><topic>Breast carcinoma</topic><topic>Cancer</topic><topic>Cancer cells</topic><topic>Cancer therapies</topic><topic>Cathepsins</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Cell division</topic><topic>Cell viability</topic><topic>Chemotherapy</topic><topic>Cytosol</topic><topic>Electric fields</topic><topic>Electromagnetic fields</topic><topic>Electromagnetism</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Fever</topic><topic>Health aspects</topic><topic>Heat</topic><topic>Heat shock proteins</topic><topic>Hsp70 protein</topic><topic>Hyperthermia</topic><topic>Immune response</topic><topic>Magnetic fields</topic><topic>Melanoma</topic><topic>Nanoparticles</topic><topic>Pancreas</topic><topic>Pancreatic carcinoma</topic><topic>Permeability</topic><topic>Pharmaceutical industry</topic><topic>Radiation therapy</topic><topic>Tumors</topic><topic>Ultrasonic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Obrador, Elena</creatorcontrib><creatorcontrib>Jihad-Jebbar, Ali</creatorcontrib><creatorcontrib>Salvador-Palmer, Rosario</creatorcontrib><creatorcontrib>López-Blanch, Rafael</creatorcontrib><creatorcontrib>Oriol-Caballo, María</creatorcontrib><creatorcontrib>Moreno-Murciano, María Paz</creatorcontrib><creatorcontrib>Navarro, Enrique A</creatorcontrib><creatorcontrib>Cibrian, Rosa</creatorcontrib><creatorcontrib>Estrela, José M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>ProQuest Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Publicly Available Content database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Obrador, Elena</au><au>Jihad-Jebbar, Ali</au><au>Salvador-Palmer, Rosario</au><au>López-Blanch, Rafael</au><au>Oriol-Caballo, María</au><au>Moreno-Murciano, María Paz</au><au>Navarro, Enrique A</au><au>Cibrian, Rosa</au><au>Estrela, José M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2023-06-29</date><risdate>2023</risdate><volume>15</volume><issue>13</issue><spage>3413</spage><pages>3413-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><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, developing more efficient heat nanomediators that may exhibit high specific absorption rates is still 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 µT, 4 h) or HT (52 °C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approximately 16%, 50%, and 21% of control 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 by combining EMFs, HT, and standard chemotherapy or EMFs, HT, and anti-Hsp70-targeted therapy. 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subjects | Apoptosis Breast carcinoma Cancer Cancer cells Cancer therapies Cathepsins Cell activation Cell cycle Cell death Cell division Cell viability Chemotherapy Cytosol Electric fields Electromagnetic fields Electromagnetism Ethylenediaminetetraacetic acid Fever Health aspects Heat Heat shock proteins Hsp70 protein Hyperthermia Immune response Magnetic fields Melanoma Nanoparticles Pancreas Pancreatic carcinoma Permeability Pharmaceutical industry Radiation therapy Tumors Ultrasonic imaging |
title | Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells |
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