Aleksandra Pawlak1, Diego DE Miguel2,3, Justyna Kutkowska4, Bożena Obmińska-Mrukowicz5, Andrzej Rapak4, Luis Martinez-Lostao6,7,8,9. 1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wroclaw, Poland aleksandra.pawlak@upwr.edu.pl. 2. Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain. 3. Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, U.K. 4. Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland. 5. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wroclaw, Poland. 6. Servicio de Inmunología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. 7. Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Instituto de Salud Carlos III, Zaragoza, Spain. 8. Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain. 9. Instituto de Nanociencia de Aragón (INA), C/ Matiano Esquillor Gomez, Zaragoza, Spain.
Abstract
BACKGROUND/AIM: Targeting the extrinsic apoptotic pathway is an interesting option for anticancer therapy. A protein which such ability is Apo2 ligand, also known as TNF-related apoptosis-inducing ligand (TRAIL). The aim of this study was to examine the possibility of sensitizing resistant CLBL-1 canine lymphoma cells to TRAIL-induced apoptosis by using flavopiridol (FVP) a cyclin-dependent kinase inhibitor (CDKs). MATERIALS AND METHODS: The CLBL-1 (canine B-cell lymphoma cell line) was used in the study. The effect of FVP and TRAIL treatment on apoptosis induction was assessed by flow cytometry and western blot. RESULTS: Although canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cells. CONCLUSION: Our results demonstrated that although canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cell line. Although further investigation is required to deepen the knowledge of TRAIL as an antitumor agent in canine cancers, our results open the door to future use of TRAIL-based treatment strategies in veterinary oncology. Copyright
BACKGROUND/AIM: Targeting the extrinsic apoptotic pathway is an interesting option for anticancer therapy. A protein which such ability is Apo2 ligand, also known as TNF-related apoptosis-inducing ligand (TRAIL). The aim of this study was to examine the possibility of sensitizing resistant CLBL-1 caninelymphoma cells to TRAIL-induced apoptosis by using flavopiridol (FVP) a cyclin-dependent kinase inhibitor (CDKs). MATERIALS AND METHODS: The CLBL-1 (canine B-cell lymphoma cell line) was used in the study. The effect of FVP and TRAIL treatment on apoptosis induction was assessed by flow cytometry and western blot. RESULTS: Although caninelymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cells. CONCLUSION: Our results demonstrated that although caninelymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cell line. Although further investigation is required to deepen the knowledge of TRAIL as an antitumor agent in caninecancers, our results open the door to future use of TRAIL-based treatment strategies in veterinary oncology. Copyright