title: PKC potentiates tyrosine kinase inhibitors STI571 and dasatinib cytotoxic effect.
abstract: OBJECTIVE
  The aim of the present study was to determine the relationship between the tyrosine kinase inhibitors, STI571 and dasatinib effects and protein kinase C (PKC) status in HMC-1(560) and HMC-1(560,816) cell lines.
  
  
  METHODS
  Viability results were obtained by two different methods: MTT and a flow cytometry with Annexin V-FITC/PI double-staining protocol. The lipid-based transfection method was used to silence PKC.
  
  
  RESULTS
  Long-term PKC activation induces apoptosis in both HMC-1 cell lines. Moreover, PKC activation potentiates STI571 and dasatinib cytotoxic effects in HMC-1(560) and HMC-1(560,816) cells, respectively, by increasing necrotic populations. To investigate this PKC effect, the role of PKCδ, an isoform intimately related with apoptotic cell death, was studied. The results obtained evidence that either STI571 or dasatinib apoptotic cell death are PKCδ-dependent. Particularly, STI571 showed less dependence to PKCδ than dasatinib.
  
  
  CONCLUSIONS
  PKCδ modulation is essential and determines mastocytosis treatment effectiveness, since STI571 and dasatinib effects are PKCδ-dependent.
authors: Pharmacology Department, School of Veterinary Sciences, University of Santiago de Compostela, University Campus, Lugo, Spain.
authors: Araceli
authors: A
authors: Tobío
authors: Pharmacology Department, School of Veterinary Sciences, University of Santiago de Compostela, University Campus, Lugo, Spain.
authors: Amparo
authors: A
authors: Alfonso
authors: Pharmacology Department, School of Veterinary Sciences, University of Santiago de Compostela, University Campus, Lugo, Spain Luis.Botana@usc.es.
authors: Luis M
authors: LM
authors: Botana
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000069439:Dasatinib; D004357:Drug Synergism; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D008415:Mastocytosis / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014162:Transfection
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000069439:Dasatinib
keywords: HMC-1; PKC; PMA; STI571; c-kit; dasatinib