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    Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway

    Access Status
    Open access via publisher
    Authors
    Edling, C.
    Selvaggi, F.
    Ghonaim, R.
    Maffucci, T.
    Falasca, Marco
    Date
    2014
    Type
    Journal Article
    
    Metadata
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    Citation
    Edling, C. and Selvaggi, F. and Ghonaim, R. and Maffucci, T. and Falasca, M. 2014. Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway. Cancer Biology and Therapy. 15 (5): pp. 524-532.
    Source Title
    Cancer Biology and Therapy
    DOI
    10.4161/cbt.28018
    ISSN
    1538-4047
    URI
    http://hdl.handle.net/20.500.11937/13886
    Collection
    • Curtin Research Publications
    Abstract

    Caffeine is a naturally occurring methylxanthine that acts as a non-selective adenosine receptor antagonist. Epidemiological studies demonstrated habitual coffee drinking to be significantly associated with liver cancer survival. We aimed to investigate the effects of caffeine and its analog CGS 15943 on hepatocellular carcinoma (HCC) and pancreatic cancer adenocarcinoma (PDAC). We demonstrate that caffeine and CGS 15943 block proliferation in HCC and PDAC cell lines by inhibiting the PI3K/Akt pathway. Importantly a kinase profiling assay reveals that CGS 15943 targets specifically the catalytic subunit of the class IB PI3K isoform (p110ƴ). These data give mechanistic insight into the action of caffeine and its analogs and they identify these compounds as promising lead compounds to develop drugs that can specifically target this PI3K isoform whose key role in cancer progression is emerging.

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