title: Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic leukaemia cells by (2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one.
abstract: OBJECTIVE
  New compounds with biological targets and less cytotoxicity to normal cells are necessary for cancer therapy. In this work ten synthetic chalcones derived from 2-naphtaldehyde were evaluated for their cytotoxic effect in murine acute lymphoblastic leukemia cells L-1210.
  
  
  METHODS
  A series of ten chalcones derived from 2-naphtaldehyde and corresponding acetophenones were prepared by aldolic condensation, using methanol as solvent under basic conditions, at room temperature for 24 h. The cell viability was determined by MTT colorimeter method. The cell cycle phase analysis was carried out by flow cytometry after propidium iodide staining. The apoptosis induction was assessed by exposure to phosphatidylserine (ANNEXIN V-FITC). Cytometric analysis was performed to evaluate the expression of p53, Bcl-2 and Bax protein. The caspase-3 expression was studied by immunoblotting analysis.
  
  
  RESULTS
  A preliminary screening of a series of ten chalcones derived from 2-naphtaldehyde showed that chalcone 8, (2E)-3-(2-naphtyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one, had the highest cytotoxic effect (IC50 of 54 microM), but not in normal human lymphocytes. To better understand the cytotoxic mechanism of chalcone 8, its effect on cell cycle and apoptosis was assessed. Our results showed that chalcone 8 caused cell cycle arrest in the G2/M phase and a significant increase in the proportion of cells in the subG0/G1 phase. Our results also demonstrated that chalcone 8 promoted a modification in Bax:Bcl-2 ratio and increased p53 expression and caspase-3 activation.
  
  
  CONCLUSIONS
  The studied chalcone 8 has cytotoxic effect against L-1210 lymphoblastic leukaemic cells, and this effect is associated with increase of p-53 and Bax expression.
authors.affiliation: Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, Brasil.
authors.forename: Fernanda Spezia
authors.initials: FS
authors.lastname: Pedrini
authors.forename: Louise Domeneghini
authors.initials: LD
authors.lastname: Chiaradia
authors.forename: Marley Aparecida
authors.initials: MA
authors.lastname: Licínio
authors.forename: Ana Carolina Rabello
authors.initials: AC
authors.lastname: de Moraes
authors.forename: Juliana Costa
authors.initials: JC
authors.lastname: Curta
authors.forename: Aline
authors.initials: A
authors.lastname: Costa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mascarello
authors.forename: Tânia Beatriz
authors.initials: TB
authors.lastname: Creczinsky-Pasa
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.forename: Rosendo Augusto
authors.initials: RA
authors.lastname: Yunes
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Santos-Silva
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis; D000447:Aldehydes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D007939:Leukemia L1210; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C556214:(2E)-3-(2-naphtyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one; D000098:Acetophenones; D000447:Aldehydes; D000970:Antineoplastic Agents; D047188:Chalcones; D009281:Naphthalenes; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C018686:2-naphthaldehyde; D053148:Caspase 3