Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: El Hajj Diab, Darine, Clerc, Pascal, Serhan, Nizar, Fourmy, Daniel, Gigoux, Véronique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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
_version_ 1783343808720666624
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
work_keys_str_mv AT elhajjdiabdarine combinedtreatmentsofmagneticintralysosomalhyperthermiawithdoxorubicinpromotessynergisticantitumoralactivity
AT clercpascal combinedtreatmentsofmagneticintralysosomalhyperthermiawithdoxorubicinpromotessynergisticantitumoralactivity
AT serhannizar combinedtreatmentsofmagneticintralysosomalhyperthermiawithdoxorubicinpromotessynergisticantitumoralactivity
AT fourmydaniel combinedtreatmentsofmagneticintralysosomalhyperthermiawithdoxorubicinpromotessynergisticantitumoralactivity
AT gigouxveronique combinedtreatmentsofmagneticintralysosomalhyperthermiawithdoxorubicinpromotessynergisticantitumoralactivity