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Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress

Skin melanoma is one of the most aggressive and difficult-to-treat human malignancies, characterized by poor survival rates, thus requiring urgent novel therapeutic approaches. Although metabolic reprogramming has represented so far, a cancer hallmark, accumulating data indicate a high plasticity of...

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Autores principales: Antunes, Fernanda, Pereira, Gustavo J. S., Saito, Renata F., Buri, Marcus V., Gagliardi, Mara, Bincoletto, Claudia, Chammas, Roger, Fimia, Gian Maria, Piacentini, Mauro, Corazzari, Marco, Smaili, Soraya Soubhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140454/
https://www.ncbi.nlm.nih.gov/pubmed/32155825
http://dx.doi.org/10.3390/cells9030640
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author Antunes, Fernanda
Pereira, Gustavo J. S.
Saito, Renata F.
Buri, Marcus V.
Gagliardi, Mara
Bincoletto, Claudia
Chammas, Roger
Fimia, Gian Maria
Piacentini, Mauro
Corazzari, Marco
Smaili, Soraya Soubhi
author_facet Antunes, Fernanda
Pereira, Gustavo J. S.
Saito, Renata F.
Buri, Marcus V.
Gagliardi, Mara
Bincoletto, Claudia
Chammas, Roger
Fimia, Gian Maria
Piacentini, Mauro
Corazzari, Marco
Smaili, Soraya Soubhi
author_sort Antunes, Fernanda
collection PubMed
description Skin melanoma is one of the most aggressive and difficult-to-treat human malignancies, characterized by poor survival rates, thus requiring urgent novel therapeutic approaches. Although metabolic reprogramming has represented so far, a cancer hallmark, accumulating data indicate a high plasticity of cancer cells in modulating cellular metabolism to adapt to a heterogeneous and continuously changing microenvironment, suggesting a novel therapeutic approach for dietary manipulation in cancer therapy. To this aim, we exposed melanoma cells to combined nutrient-restriction/sorafenib. Results indicate that cell death was efficiently induced, with apoptosis representing the prominent feature. In contrast, autophagy was blocked in the final stage by this treatment, similarly to chloroquine, which also enhanced melanoma cell sensitization to combined treatment. Energy stress was evidenced by associated treatment with mitochondrial dysfunction and glycolysis impairment, suggesting metabolic stress determining melanoma cell death. A reduction of tumor growth after cycles of intermittent fasting together with sorafenib treatment was also observed in vivo, reinforcing that the nutrient shortage can potentiate anti-melanoma therapy. Our findings showed that the restriction of nutrients by intermittent fasting potentiates the effects of sorafenib due to the modulation of cellular metabolism, suggesting that it is possible to harness the energy of cancer cells for the treatment of melanoma.
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spelling pubmed-71404542020-04-13 Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress Antunes, Fernanda Pereira, Gustavo J. S. Saito, Renata F. Buri, Marcus V. Gagliardi, Mara Bincoletto, Claudia Chammas, Roger Fimia, Gian Maria Piacentini, Mauro Corazzari, Marco Smaili, Soraya Soubhi Cells Article Skin melanoma is one of the most aggressive and difficult-to-treat human malignancies, characterized by poor survival rates, thus requiring urgent novel therapeutic approaches. Although metabolic reprogramming has represented so far, a cancer hallmark, accumulating data indicate a high plasticity of cancer cells in modulating cellular metabolism to adapt to a heterogeneous and continuously changing microenvironment, suggesting a novel therapeutic approach for dietary manipulation in cancer therapy. To this aim, we exposed melanoma cells to combined nutrient-restriction/sorafenib. Results indicate that cell death was efficiently induced, with apoptosis representing the prominent feature. In contrast, autophagy was blocked in the final stage by this treatment, similarly to chloroquine, which also enhanced melanoma cell sensitization to combined treatment. Energy stress was evidenced by associated treatment with mitochondrial dysfunction and glycolysis impairment, suggesting metabolic stress determining melanoma cell death. A reduction of tumor growth after cycles of intermittent fasting together with sorafenib treatment was also observed in vivo, reinforcing that the nutrient shortage can potentiate anti-melanoma therapy. Our findings showed that the restriction of nutrients by intermittent fasting potentiates the effects of sorafenib due to the modulation of cellular metabolism, suggesting that it is possible to harness the energy of cancer cells for the treatment of melanoma. MDPI 2020-03-06 /pmc/articles/PMC7140454/ /pubmed/32155825 http://dx.doi.org/10.3390/cells9030640 Text en © 2020 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
Antunes, Fernanda
Pereira, Gustavo J. S.
Saito, Renata F.
Buri, Marcus V.
Gagliardi, Mara
Bincoletto, Claudia
Chammas, Roger
Fimia, Gian Maria
Piacentini, Mauro
Corazzari, Marco
Smaili, Soraya Soubhi
Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress
title Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress
title_full Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress
title_fullStr Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress
title_full_unstemmed Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress
title_short Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress
title_sort effective synergy of sorafenib and nutrient shortage in inducing melanoma cell death through energy stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140454/
https://www.ncbi.nlm.nih.gov/pubmed/32155825
http://dx.doi.org/10.3390/cells9030640
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