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

• Published in: Journal of pharmacy and pharmacology Vol. 62; no. 9; p. 1128
• Main Authors: Pedrini, Fernanda Spezia, Chiaradia, Louise Domeneghini, Licínio, Marley Aparecida, de Moraes, Ana Carolina Rabello, Curta, Juliana Costa, Costa, Aline, Mascarello, Alessandra, Creczinsky-Pasa, Tânia Beatriz, Nunes, Ricardo José, Yunes, Rosendo Augusto, Santos-Silva, Maria Cláudia
• Format: Journal Article
• Language: English
• Published: England 01.09.2010
• Subjects: Acetophenones - chemical synthesis; Aldehydes - pharmacology; Aldehydes - therapeutic use; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Caspase 3 - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Chalcones - chemical synthesis; Chalcones - pharmacology; Chalcones - therapeutic use; Leukemia - drug therapy; Leukemia - metabolism; Leukemia L1210; Lymphocytes - drug effects; Mice; Naphthalenes - pharmacology; Naphthalenes - therapeutic use; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Proto-Oncogene Proteins c-bcl-2 - metabolism; Tumor Suppressor Protein p53 - metabolism
• ISSN: 2042-7158
• DOI: 10.1111/j.2042-7158.2010.01141.x

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. 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. 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. 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.