title: Benznidazole modulates cell proliferation in acute leukemia cells.
abstract: BACKGROUND
  We have previously reported that benznidazole (BZL), known for its trypanocidal action, has anti-proliferative activity against different cell lines like HeLa and Raw 264.7 among others. At the moment, it has not been reported if the anti-proliferative effect of BZL is similar for non-adherent hematopoietic cells like was reported for adherent cancer cell lines.
  
  
  OBJECTIVE
  We aimed to investigate the efficacy of BZL on the growth of the leukemic cell lines THP-1 and OCI/AML3.
  
  
  METHODS
  We evaluated cell proliferation by [³H]-thymidine incorporation and MTT reduction as well as cell death by lactate dehydrogenase (LDH) activity. We assessed apoptosis by flow cytometry for detection of annexin V-positive and propidium iodide-negative cells, along with nuclear morphology by diamidino-2-phenolindole (DAPI) staining. Western blot studies were performed to evaluate changes in cell cycle proteins in BZL-treated cells.
  
  
  RESULTS
  BZL significantly reduced proliferation of both cell lines without inducing cell death. Likewise it produced no significant differences in apoptosis between treated cells and controls. In addition, flow cytometry analysis indicated that BZL caused a larger number of THP-1 cells in G0/G1 phase and a smaller number of cells in S phase than controls. This was accompanied with an increase in the expression of the CDK inhibitor p27 and of cyclin D1, with no significant differences in the protein levels of CDK1, CDK2, CDK4, cyclins E, A and B as compared to controls.
  
  
  CONCLUSIONS
  BZL inhibits the proliferation of leukemic non-adherent cells by controlling cell cycle at G0/G1 cell phase through up-regulation of p27.
authors.affiliation: Instituto de Inmunología, Facultad Ciencias Médicas, Universidad Nacional Rosario, Rosario, Argentina.
authors.forename: Karina Lucrecia
authors.initials: KL
authors.lastname: Calvo
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ronco
authors.forename: Nélida Inés
authors.initials: NI
authors.lastname: Noguera
authors.forename: Fabiana
authors.initials: F
authors.lastname: García
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D016213:Cyclins / Q000096:biosynthesis; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009593:Nitroimidazoles / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*
chemical_list: D016213:Cyclins; D009363:Neoplasm Proteins; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; C009999:benzonidazole