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Analyses of the combination of 6-MP and dasatinib in cell culture

A major tenet of cancer therapeutics is that combinations of anticancer agents with different mechanisms of action and different toxicities may be effective treatment regimens. Evaluation of additivity/synergy in cell culture may be used to identify drug combination opportunities and to assess risk...

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Detalles Bibliográficos
Autores principales: KAUR, GURMEET, BEHRSING, HOLGER, PARCHMENT, RALPH E., MILLIN, MYRTLE DAVIS, TEICHER, BEVERLY A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742163/
https://www.ncbi.nlm.nih.gov/pubmed/23652925
http://dx.doi.org/10.3892/ijo.2013.1930
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author KAUR, GURMEET
BEHRSING, HOLGER
PARCHMENT, RALPH E.
MILLIN, MYRTLE DAVIS
TEICHER, BEVERLY A.
author_facet KAUR, GURMEET
BEHRSING, HOLGER
PARCHMENT, RALPH E.
MILLIN, MYRTLE DAVIS
TEICHER, BEVERLY A.
author_sort KAUR, GURMEET
collection PubMed
description A major tenet of cancer therapeutics is that combinations of anticancer agents with different mechanisms of action and different toxicities may be effective treatment regimens. Evaluation of additivity/synergy in cell culture may be used to identify drug combination opportunities and to assess risk of additive/synergistic toxicity. The combination of 6-mercaptopurine and dasatinib was assessed for additivity/synergy using the combination index (CI) method and a response surface method in six human tumor cell lines including MCF-7 and MDA-MB-468 breast cancer, NCI-H23 and NCI-H460 non-small cell lung cancer, and A498 and 786-O renal cell cancer, based on two experimental end-points: ATP content and colony formation. Clonal colony formation by human bone marrow CFU-GM was used to assess risk of enhanced toxicity. The concentration ranges tested for each drug were selected to encompass the clinical C(max) concentrations. The combination regimens were found to be additive to sub-additive by both methods of data analysis, but synergy was not detected. The non-small cell lung cancer cell lines were the most responsive among the tumor lines tested and the renal cell carcinoma lines were the least responsive. The bone marrows CFU-GM were more sensitive to the combination regimens than were the tumor cell lines. Based upon these data, it appears that the possibility of enhanced efficacy from combining 6-mercaptopurine (6-MP) and dasatinib would be associated with increased risk of severe bone marrow toxicity, so the combination is unlikely to provide a therapeutic advantage for treating solid tumor patients where adequate bone marrow function must be preserved.
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spelling pubmed-37421632013-08-14 Analyses of the combination of 6-MP and dasatinib in cell culture KAUR, GURMEET BEHRSING, HOLGER PARCHMENT, RALPH E. MILLIN, MYRTLE DAVIS TEICHER, BEVERLY A. Int J Oncol Articles A major tenet of cancer therapeutics is that combinations of anticancer agents with different mechanisms of action and different toxicities may be effective treatment regimens. Evaluation of additivity/synergy in cell culture may be used to identify drug combination opportunities and to assess risk of additive/synergistic toxicity. The combination of 6-mercaptopurine and dasatinib was assessed for additivity/synergy using the combination index (CI) method and a response surface method in six human tumor cell lines including MCF-7 and MDA-MB-468 breast cancer, NCI-H23 and NCI-H460 non-small cell lung cancer, and A498 and 786-O renal cell cancer, based on two experimental end-points: ATP content and colony formation. Clonal colony formation by human bone marrow CFU-GM was used to assess risk of enhanced toxicity. The concentration ranges tested for each drug were selected to encompass the clinical C(max) concentrations. The combination regimens were found to be additive to sub-additive by both methods of data analysis, but synergy was not detected. The non-small cell lung cancer cell lines were the most responsive among the tumor lines tested and the renal cell carcinoma lines were the least responsive. The bone marrows CFU-GM were more sensitive to the combination regimens than were the tumor cell lines. Based upon these data, it appears that the possibility of enhanced efficacy from combining 6-mercaptopurine (6-MP) and dasatinib would be associated with increased risk of severe bone marrow toxicity, so the combination is unlikely to provide a therapeutic advantage for treating solid tumor patients where adequate bone marrow function must be preserved. D.A. Spandidos 2013-05-02 /pmc/articles/PMC3742163/ /pubmed/23652925 http://dx.doi.org/10.3892/ijo.2013.1930 Text en Copyright © 2013, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
KAUR, GURMEET
BEHRSING, HOLGER
PARCHMENT, RALPH E.
MILLIN, MYRTLE DAVIS
TEICHER, BEVERLY A.
Analyses of the combination of 6-MP and dasatinib in cell culture
title Analyses of the combination of 6-MP and dasatinib in cell culture
title_full Analyses of the combination of 6-MP and dasatinib in cell culture
title_fullStr Analyses of the combination of 6-MP and dasatinib in cell culture
title_full_unstemmed Analyses of the combination of 6-MP and dasatinib in cell culture
title_short Analyses of the combination of 6-MP and dasatinib in cell culture
title_sort analyses of the combination of 6-mp and dasatinib in cell culture
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742163/
https://www.ncbi.nlm.nih.gov/pubmed/23652925
http://dx.doi.org/10.3892/ijo.2013.1930
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