title: Pharmacological agents with inherent anti-autophagic activity improve the cytotoxicity of imatinib.
abstract: Resistance to tyrosine kinase inhibitors (TKIs) remains a limitation to the treatment of chronic myeloid leukaemia (CML), due in part, to the induction of autophagy. We examined whether disruption of autophagy with the pharmacological agents, brefeldin A, vincristine and chloroquine, improves the cytotoxicity of imatinib. In K562 CML cells, all drugs tested, in combination with imatinib impaired the expression or cellular distribution of LC3 and Beclin 1 (autophagy markers) and reduced the recovery of cells following drug withdrawal. The combination of imatinib and an agent that impedes autophagy demonstrates impressive potential as a more curative regime for CML.
authors.affiliation: Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College Cork, Cork, Ireland.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Crowley
authors.forename: Tracey R
authors.initials: TR
authors.lastname: O'Donovan
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Nyhan
authors.forename: Sharon L
authors.initials: SL
authors.lastname: McKenna
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D020126:Brefeldin A / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D020126:Brefeldin A; D014750:Vincristine; D002738:Chloroquine; D000068877:Imatinib Mesylate