Flavopiridol Strongly Sensitizes Canine Lymphoma Cells to TRAIL-induced Apoptosis

Anticancer Res. 2017 Dec;37(12):6655-6665. doi: 10.21873/anticanres.12123.

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.

Keywords: TRAIL; apoptosis; canine lymphoma cells; flavopiridol.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Dog Diseases / metabolism
  • Dog Diseases / pathology
  • Dogs
  • Drug Resistance, Neoplasm / drug effects
  • Drug Synergism
  • Flavonoids / pharmacology*
  • Flow Cytometry
  • Humans
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Piperidines / pharmacology*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

  • Antineoplastic Agents
  • Flavonoids
  • Piperidines
  • TNF-Related Apoptosis-Inducing Ligand
  • alvocidib