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

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 159...

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Main Authors: Edling, C., Selvaggi, F., Ghonaim, R., Maffucci, T., Falasca, Marco
Format: Journal Article
Published: Landes Bioscience 2014
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/13886
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author Edling, C.
Selvaggi, F.
Ghonaim, R.
Maffucci, T.
Falasca, Marco
author_facet Edling, C.
Selvaggi, F.
Ghonaim, R.
Maffucci, T.
Falasca, Marco
author_sort Edling, C.
building Curtin Institutional Repository
collection Online Access
description 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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institution Curtin University Malaysia
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last_indexed 2025-11-14T07:05:31Z
publishDate 2014
publisher Landes Bioscience
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spelling curtin-20.500.11937-138862017-09-13T15:01:41Z Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway Edling, C. Selvaggi, F. Ghonaim, R. Maffucci, T. Falasca, Marco phosphoinositide 3-kinase caffeine CGS 15943 pancreatic ductal adenocarcinoma hepatocellular carcinoma 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/13886 10.4161/cbt.28018 Landes Bioscience unknown
spellingShingle phosphoinositide 3-kinase
caffeine
CGS 15943
pancreatic ductal adenocarcinoma
hepatocellular carcinoma
Edling, C.
Selvaggi, F.
Ghonaim, R.
Maffucci, T.
Falasca, Marco
Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway
title Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway
title_full Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway
title_fullStr Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway
title_full_unstemmed Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway
title_short Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway
title_sort caffeine and the analog cgs 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/akt pathway
topic phosphoinositide 3-kinase
caffeine
CGS 15943
pancreatic ductal adenocarcinoma
hepatocellular carcinoma
url http://hdl.handle.net/20.500.11937/13886