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Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells

Mono-targeting by imatinib as a main antitumor agent does not always accomplish complete cancer suppression. 2,5-dimethyl-celecoxib (DMC) is a close structural analog of the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, that lacks COX-2 inhibitory function. In this study, we aimed to show...

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Autores principales: Atari-Hajipirloo, Somayeh, Nikanfar, Saba, Heydari, Amir, Kheradmand, Fatemeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333482/
https://www.ncbi.nlm.nih.gov/pubmed/28255316
http://dx.doi.org/10.4103/1735-5362.199049
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author Atari-Hajipirloo, Somayeh
Nikanfar, Saba
Heydari, Amir
Kheradmand, Fatemeh
author_facet Atari-Hajipirloo, Somayeh
Nikanfar, Saba
Heydari, Amir
Kheradmand, Fatemeh
author_sort Atari-Hajipirloo, Somayeh
collection PubMed
description Mono-targeting by imatinib as a main antitumor agent does not always accomplish complete cancer suppression. 2,5-dimethyl-celecoxib (DMC) is a close structural analog of the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, that lacks COX-2 inhibitory function. In this study, we aimed to show the apoptotic effects of imatinib in combination with DMC in human HT-29 colorectal cancer (CRC) cells. HT-29 CRC cells were treated with IC(50) dose of imatinib (6.60 μM), DMC (23.45 μM), and their combination (half dose of IC(50)) for 24 h. The caspase-3 activity was estimated with colorimetric kit. The caspase-3 gene expression was evaluated by real-time PCR method. There was a significant up-regulation in caspase-3 enzyme activity and caspase-3 expression by imatinib and its half dose combination with DMC as compared to control. As a summary, the results of this study strongly suggest that half dose combination of imatinib with DMC induced apoptosis as potent as full dose imatinib in human HT-29 CRC cells, while minimizing undesired side effects related to imatinib mono-therapy. This study also pointed towards possible caspase-dependent actions of imatinib and DMC.
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spelling pubmed-53334822017-03-02 Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells Atari-Hajipirloo, Somayeh Nikanfar, Saba Heydari, Amir Kheradmand, Fatemeh Res Pharm Sci Original Article Mono-targeting by imatinib as a main antitumor agent does not always accomplish complete cancer suppression. 2,5-dimethyl-celecoxib (DMC) is a close structural analog of the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, that lacks COX-2 inhibitory function. In this study, we aimed to show the apoptotic effects of imatinib in combination with DMC in human HT-29 colorectal cancer (CRC) cells. HT-29 CRC cells were treated with IC(50) dose of imatinib (6.60 μM), DMC (23.45 μM), and their combination (half dose of IC(50)) for 24 h. The caspase-3 activity was estimated with colorimetric kit. The caspase-3 gene expression was evaluated by real-time PCR method. There was a significant up-regulation in caspase-3 enzyme activity and caspase-3 expression by imatinib and its half dose combination with DMC as compared to control. As a summary, the results of this study strongly suggest that half dose combination of imatinib with DMC induced apoptosis as potent as full dose imatinib in human HT-29 CRC cells, while minimizing undesired side effects related to imatinib mono-therapy. This study also pointed towards possible caspase-dependent actions of imatinib and DMC. Medknow Publications & Media Pvt Ltd 2017-02 /pmc/articles/PMC5333482/ /pubmed/28255316 http://dx.doi.org/10.4103/1735-5362.199049 Text en Copyright: © 2017 Research in Pharmaceutical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Atari-Hajipirloo, Somayeh
Nikanfar, Saba
Heydari, Amir
Kheradmand, Fatemeh
Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells
title Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells
title_full Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells
title_fullStr Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells
title_full_unstemmed Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells
title_short Imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human HT-29 colorectal cancer cells
title_sort imatinib and its combination with 2,5-dimethyl-celecoxibinduces apoptosis of human ht-29 colorectal cancer cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333482/
https://www.ncbi.nlm.nih.gov/pubmed/28255316
http://dx.doi.org/10.4103/1735-5362.199049
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