Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T3151 Bcr-Abl mutant by a redox-mediated mechanism

被引：9

作者：

Corrado, Chiara ^{[1
]}

Raimondo, Stefania ^{[1
]}

Flugy, Anna Maria ^{[1
]}

Fontana, Simona ^{[1
]}

Santoro, Alessandra ^{[2
]}

Stassi, Giorgio ^{[3
]}

Marfia, Anna ^{[2
]}

Iovino, Flora ^{[3
]}

Arlinghaus, Ralph ^{[4
]}

Kohn, Elise C. ^{[5
]}

De Leo, Giacomo ^{[1
]}

Alessandro, Riccardo ^{[1
]}

机构：

[1] Univ Palermo, Dipartimento Biopatol & Biotecnol Med & Forensi, Sez Biol & Genet, I-90133 Palermo, Italy

[2] AO V Cervello, Lab Ematol, Dipartimento Ric Clin & Biotecnol, Palermo, Italy

[3] Dipartimento Sci Chirurg & Oncol, Palermo, Italy

[4] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[5] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

来源：

CANCER LETTERS | 2011年 / 300卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Chronic myelogenous leukemia (CML); Carboxy amidotriazole (CAI); Drug resistance; Reactive-oxygen species (ROS); CHRONIC MYELOGENOUS LEUKEMIA; REACTIVE OXYGEN; IN-VITRO; TYROSINE KINASE; CANCER-CELLS; INDUCED APOPTOSIS; BCR/ABL; DEATH; ROS; ACTIVATION;

D O I：

10.1016/j.canlet.2010.10.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutation of the Bcr-Abl oncoprotein is one of most frequent mechanisms by which chronic myelogenous leukemia (CML) cells become resistant to imatinib Here we show that treatment of cell lines harbouring wild type or mutant BCR-ABL with carboxyamidotriazole (CAI) a calcium influx and signal transduction inhibitor inhibits cell growth the expression of Bcr-Abl and its downstream signalling and Induces apoptosis Moreover we show that CAI acts by increasing intracellular ROS Clinically ignificant CAI has also inhibitory effects on T315I Bcr-Abl mutant a mutation that causes CML cells to become insensitive to imatinib and second generation abl kinase inhibitors (C) 2010 Elsevier Ireland Ltd All rights reserved

引用

收藏

页码：205 / 214

页数：10

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