咖啡因及类似物CGS 15943通过靶向磷酸肌醇3激酶/蛋白激酶B信号通路抑制癌细胞生长。
Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway.
作者信息
Edling Charlotte E, Selvaggi Federico, Ghonaim Ragheda, Maffucci Tania, Falasca Marco
机构信息
Queen Mary University of London; Blizard Institute; Barts and The London School of Medicine and Dentistry; Inositide Signalling Group; London, UK.
出版信息
Cancer Biol Ther. 2014 May;15(5):524-32. doi: 10.4161/cbt.28018. Epub 2014 Feb 12.
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 (p110γ). 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.
摘要
咖啡因是一种天然存在的甲基黄嘌呤，可作为非选择性腺苷受体拮抗剂。流行病学研究表明，习惯性饮用咖啡与肝癌生存率显著相关。我们旨在研究咖啡因及其类似物CGS 15943对肝细胞癌（HCC）和胰腺腺癌（PDAC）的影响。我们证明，咖啡因和CGS 15943通过抑制PI3K/Akt途径来阻断HCC和PDAC细胞系的增殖。重要的是，激酶谱分析显示CGS 15943特异性靶向IB类PI3K亚型（p110γ）的催化亚基。这些数据为咖啡因及其类似物的作用提供了机制性见解，并将这些化合物确定为有前景的先导化合物，可用于开发能够特异性靶向这种在癌症进展中发挥关键作用的PI3K亚型的药物。
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