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Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells
Ovarian cancer is an aggressive and lethal cancer usually treated by cytoreductive surgery followed by chemotherapy. Unfortunately, after an initial response, many patients relapse owing mainly to the development of resistance against the standard chemotherapy regime, carboplatin/paclitaxel, which i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908290/ https://www.ncbi.nlm.nih.gov/pubmed/29682189 http://dx.doi.org/10.18632/oncotarget.24708 |
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author | Catanzaro, Daniela Nicolosi, Silvia Cocetta, Veronica Salvalaio, Marika Pagetta, Andrea Ragazzi, Eugenio Montopoli, Monica Pasut, Gianfranco |
author_facet | Catanzaro, Daniela Nicolosi, Silvia Cocetta, Veronica Salvalaio, Marika Pagetta, Andrea Ragazzi, Eugenio Montopoli, Monica Pasut, Gianfranco |
author_sort | Catanzaro, Daniela |
collection | PubMed |
description | Ovarian cancer is an aggressive and lethal cancer usually treated by cytoreductive surgery followed by chemotherapy. Unfortunately, after an initial response, many patients relapse owing mainly to the development of resistance against the standard chemotherapy regime, carboplatin/paclitaxel, which is also affected by heavy side effects. In view to addressing such issues here, an association of liposomal cisplatin with 6-amino nicotinamide is investigated. It is known that resistant cells increase their demand for glucose, which is partially redirected toward the pentose phosphate pathway (PPP). Interestingly, we have found that also a cisplatin-resistant subclone of the ovarian cancer cells IGROV1 switch their metabolism toward the glycolytic pathway and rely on PPP to elude cisplatin cytotoxicity. The drug 6-amino nicotinamide, an inhibitor of the enzyme glucose-6-phosphate dehydrogenase (the rate-limiting step of the PPP) can restore the sensitivity of resistant cells to cisplatin. Then, to reduce the toxicity of cisplatin and prolong its action, a lyophilized stealth liposomal formulation of cisplatin was developed. The combination treatment of liposomal cisplatin and 6-amino nicotinamide showed promising cytotoxic activities in drug-resistant cells and a prolonged pharmacokinetics in rats, thus opening the way for a new therapeutic option against ovarian cancer. |
format | Online Article Text |
id | pubmed-5908290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59082902018-04-20 Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells Catanzaro, Daniela Nicolosi, Silvia Cocetta, Veronica Salvalaio, Marika Pagetta, Andrea Ragazzi, Eugenio Montopoli, Monica Pasut, Gianfranco Oncotarget Research Paper Ovarian cancer is an aggressive and lethal cancer usually treated by cytoreductive surgery followed by chemotherapy. Unfortunately, after an initial response, many patients relapse owing mainly to the development of resistance against the standard chemotherapy regime, carboplatin/paclitaxel, which is also affected by heavy side effects. In view to addressing such issues here, an association of liposomal cisplatin with 6-amino nicotinamide is investigated. It is known that resistant cells increase their demand for glucose, which is partially redirected toward the pentose phosphate pathway (PPP). Interestingly, we have found that also a cisplatin-resistant subclone of the ovarian cancer cells IGROV1 switch their metabolism toward the glycolytic pathway and rely on PPP to elude cisplatin cytotoxicity. The drug 6-amino nicotinamide, an inhibitor of the enzyme glucose-6-phosphate dehydrogenase (the rate-limiting step of the PPP) can restore the sensitivity of resistant cells to cisplatin. Then, to reduce the toxicity of cisplatin and prolong its action, a lyophilized stealth liposomal formulation of cisplatin was developed. The combination treatment of liposomal cisplatin and 6-amino nicotinamide showed promising cytotoxic activities in drug-resistant cells and a prolonged pharmacokinetics in rats, thus opening the way for a new therapeutic option against ovarian cancer. Impact Journals LLC 2018-03-30 /pmc/articles/PMC5908290/ /pubmed/29682189 http://dx.doi.org/10.18632/oncotarget.24708 Text en Copyright: © 2018 Catanzaro et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Catanzaro, Daniela Nicolosi, Silvia Cocetta, Veronica Salvalaio, Marika Pagetta, Andrea Ragazzi, Eugenio Montopoli, Monica Pasut, Gianfranco Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
title | Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
title_full | Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
title_fullStr | Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
title_full_unstemmed | Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
title_short | Cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
title_sort | cisplatin liposome and 6-amino nicotinamide combination to overcome drug resistance in ovarian cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908290/ https://www.ncbi.nlm.nih.gov/pubmed/29682189 http://dx.doi.org/10.18632/oncotarget.24708 |
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