Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr-Abl mutant by a redox-mediated mechanism.

Riccardo Alessandro, Chiara Corrado, Anna Maria Flugy Pape', Flora Iovino, Giorgio Stassi, Giacomo De Leo, Simona Fontana, Stefania Raimondo, Giacomo De Leo, Anna Marfia, Chiara Corrado, Elise C. Kohn, Stefania Raimondo, Alessandra Santoro, Anna Maria Flugy, Riccardo Alessandro, Giorgio Stassi, Simona Fontana, Ralph Arlinghaus, Flora Iovino

Risultato della ricerca: Articlepeer review

7 Citazioni (Scopus)

Abstract

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 treat- ment of cell lines harbouring wild type or mutant BCR–ABL with carboxyamidotriazole (CAI), a calcium influx and signal transduction inhibitor, inhibits cell growth, the expres- sion of Bcr–Abl and its downstream signalling, and induces apoptosis. Moreover, we show that CAI acts by increasing intracellular ROS. Clinically significant, 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.
Lingua originaleUndefined/Unknown
pagine (da-a)205-214
Numero di pagine10
RivistaCancer Letters
Volume300
Stato di pubblicazionePublished - 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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