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Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity
Doxorubicin is a cytotoxic drug used for the treatment of many cancer types. However, its significant dose-related adverse effects including cardiotoxicity may hamper its efficiency. Moreover, the multidrug resistance that appears during treatments limits anti-cancer therapies. Hyperthermia has been...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071107/ https://www.ncbi.nlm.nih.gov/pubmed/29954075 http://dx.doi.org/10.3390/nano8070468 |
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author | El Hajj Diab, Darine Clerc, Pascal Serhan, Nizar Fourmy, Daniel Gigoux, Véronique |
author_facet | El Hajj Diab, Darine Clerc, Pascal Serhan, Nizar Fourmy, Daniel Gigoux, Véronique |
author_sort | El Hajj Diab, Darine |
collection | PubMed |
description | Doxorubicin is a cytotoxic drug used for the treatment of many cancer types. However, its significant dose-related adverse effects including cardiotoxicity may hamper its efficiency. Moreover, the multidrug resistance that appears during treatments limits anti-cancer therapies. Hyperthermia has been introduced as an adjuvant anti-cancer therapy and presents promising opportunities especially in combination with chemotherapy. However, hyperthermia methods including standard magnetic hyperthermia do not discriminate between the target and the surrounding normal tissues and can lead to side effects. In this context, a Magnetic Intra-Lysosomal Hyperthermia (MILH) approach, which occurs without perceptible temperature rise, has been developed. We previously showed that minute amounts of iron oxide magnetic nanoparticles targeting the gastrin receptor (CCK2R) are internalized by cancer cells through a CCK2R-dependent physiological process, accumulated into their lysosomes and kill cancer cells upon high frequency alternating magnetic field (AMF) application through lysosomal cell death. Here, we show that the combination of MILH with doxorubicin increases the efficiency of the eradication of endocrine tumor cells with synergism. We also demonstrate that these two treatments activate two different cell death pathways that are respectively dependent on Caspase-1 and Caspase-3 activation. These findings will result in the development of new anti-tumoral, intra-lysosomal-thermo/chemotherapy with better curative effects than chemotherapy alone and that are devoid of adverse effects linked to standard hyperthermia approaches. |
format | Online Article Text |
id | pubmed-6071107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60711072018-08-09 Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity El Hajj Diab, Darine Clerc, Pascal Serhan, Nizar Fourmy, Daniel Gigoux, Véronique Nanomaterials (Basel) Article Doxorubicin is a cytotoxic drug used for the treatment of many cancer types. However, its significant dose-related adverse effects including cardiotoxicity may hamper its efficiency. Moreover, the multidrug resistance that appears during treatments limits anti-cancer therapies. Hyperthermia has been introduced as an adjuvant anti-cancer therapy and presents promising opportunities especially in combination with chemotherapy. However, hyperthermia methods including standard magnetic hyperthermia do not discriminate between the target and the surrounding normal tissues and can lead to side effects. In this context, a Magnetic Intra-Lysosomal Hyperthermia (MILH) approach, which occurs without perceptible temperature rise, has been developed. We previously showed that minute amounts of iron oxide magnetic nanoparticles targeting the gastrin receptor (CCK2R) are internalized by cancer cells through a CCK2R-dependent physiological process, accumulated into their lysosomes and kill cancer cells upon high frequency alternating magnetic field (AMF) application through lysosomal cell death. Here, we show that the combination of MILH with doxorubicin increases the efficiency of the eradication of endocrine tumor cells with synergism. We also demonstrate that these two treatments activate two different cell death pathways that are respectively dependent on Caspase-1 and Caspase-3 activation. These findings will result in the development of new anti-tumoral, intra-lysosomal-thermo/chemotherapy with better curative effects than chemotherapy alone and that are devoid of adverse effects linked to standard hyperthermia approaches. MDPI 2018-06-27 /pmc/articles/PMC6071107/ /pubmed/29954075 http://dx.doi.org/10.3390/nano8070468 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article El Hajj Diab, Darine Clerc, Pascal Serhan, Nizar Fourmy, Daniel Gigoux, Véronique Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity |
title | Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity |
title_full | Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity |
title_fullStr | Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity |
title_full_unstemmed | Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity |
title_short | Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity |
title_sort | combined treatments of magnetic intra-lysosomal hyperthermia with doxorubicin promotes synergistic anti-tumoral activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071107/ https://www.ncbi.nlm.nih.gov/pubmed/29954075 http://dx.doi.org/10.3390/nano8070468 |
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