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Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis
The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently upregulated in human cancer. Activation of this pathway has been reported to be associated with resistance to various chemotherapeutical agents. We here used a chemical biology/chemical informatic approach to identify apoptotic mecha...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701489/ https://www.ncbi.nlm.nih.gov/pubmed/19568785 http://dx.doi.org/10.1007/s12154-009-0017-7 |
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author | Berndtsson, Maria Hernlund, Emma Shoshan, Maria C. Linder, Stig |
author_facet | Berndtsson, Maria Hernlund, Emma Shoshan, Maria C. Linder, Stig |
author_sort | Berndtsson, Maria |
collection | PubMed |
description | The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently upregulated in human cancer. Activation of this pathway has been reported to be associated with resistance to various chemotherapeutical agents. We here used a chemical biology/chemical informatic approach to identify apoptotic mechanisms that are insensitive to activation of the PI3K/AKT pathway. The National Cancer Institute (NCI) Mechanistic Set drug library was screened for agents that induce apoptosis in colon carcinoma cells expressing a constitutively active form of AKT1. The cytotoxicity screening data available as self-organized maps at the Developmental Therapeutics Program (DTP) of the NCI was then used to classify the identified compounds according to mechanism of action. The results showed that drugs that interfere with the mitotic process induce apoptosis which is comparatively insensitive to constitutive AKT1 activity. The conditional screening approach described here is expected to be useful for identifying relationships between the state of activation of signaling pathways and sensitivity to anticancer agents. |
format | Text |
id | pubmed-2701489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-27014892009-06-25 Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis Berndtsson, Maria Hernlund, Emma Shoshan, Maria C. Linder, Stig J Chem Biol Original Article The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently upregulated in human cancer. Activation of this pathway has been reported to be associated with resistance to various chemotherapeutical agents. We here used a chemical biology/chemical informatic approach to identify apoptotic mechanisms that are insensitive to activation of the PI3K/AKT pathway. The National Cancer Institute (NCI) Mechanistic Set drug library was screened for agents that induce apoptosis in colon carcinoma cells expressing a constitutively active form of AKT1. The cytotoxicity screening data available as self-organized maps at the Developmental Therapeutics Program (DTP) of the NCI was then used to classify the identified compounds according to mechanism of action. The results showed that drugs that interfere with the mitotic process induce apoptosis which is comparatively insensitive to constitutive AKT1 activity. The conditional screening approach described here is expected to be useful for identifying relationships between the state of activation of signaling pathways and sensitivity to anticancer agents. Springer-Verlag 2009-03-31 2009-06 /pmc/articles/PMC2701489/ /pubmed/19568785 http://dx.doi.org/10.1007/s12154-009-0017-7 Text en © Springer-Verlag 2009 |
spellingShingle | Original Article Berndtsson, Maria Hernlund, Emma Shoshan, Maria C. Linder, Stig Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis |
title | Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis |
title_full | Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis |
title_fullStr | Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis |
title_full_unstemmed | Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis |
title_short | Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis |
title_sort | conditional drug screening shows that mitotic inhibitors induce akt/pkb-insensitive apoptosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701489/ https://www.ncbi.nlm.nih.gov/pubmed/19568785 http://dx.doi.org/10.1007/s12154-009-0017-7 |
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