Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-06

AUTHORS

Maria Berndtsson, Emma Hernlund, Maria C. Shoshan, Stig Linder

ABSTRACT

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. More... »

PAGES

81-87

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12154-009-0017-7

DOI

http://dx.doi.org/10.1007/s12154-009-0017-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023384873

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19568785


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