title: Investigation of cellular mechanisms involved in apoptosis induced by a synthetic naphthylchalcone in acute leukemia cell lines.
abstract: We have previously reported the cytotoxic effects of chalcone A1, derived from 1-naphthaldehyde, in leukemia cell lines. On the basis of these findings, the main aim of this study was to elucidate some of the molecular mechanisms involved in apoptosis induced by chalcone A1 toward K562 and Jurkat cells. In both cell lines, chalcone A1 decreased the mitochondrial membrane potential, increased the expression of Bax proapoptotic protein, and decreased the expression of Bcl-2 antiapoptotic protein (resulting in the inversion of the Bcl-2/Bax ratio), which indicates the involvement of the intrinsic pathway. In addition, chalcone A1 increased the expression of FasR in Jurkat cells, which also indicates the involvement of the extrinsic pathway in this cell line. The results also showed an increased expression of effector caspase-3 and cleaved PARP-1 and a decreased expression of IAP protein survivin, which are consistent with apoptotic cell death. The decreased expression of Ki67 suggests that the mechanism involved in cell death induced by chalcone A1 also involves a decrease in cell proliferation. In ex-vivo experiments, chalcone A1 reduced the cell viability of blast cells collected from eight patients with different types of acute leukemia, confirming the cytotoxicity results found in vitro. The results obtained so far are very promising and further studies need to be carried out so that chalcone A1 can be used as a prototype for the development of new antileukemia agents.
authors.affiliation: aExperimental Oncology Laboratory, Department of Clinical Analysis bStructure and Activity Laboratory, Department of Chemistry cPost-Graduation Program in Pharmacy-PGFAR, Federal Universtiy of Santa Catarina, Campus Trindade, CEP: 88040-900, Florianópolis - Santa Catarina, Brazil.
authors.forename: Mariana Franzoni
authors.initials: MF
authors.lastname: Maioral
authors.forename: Ana Carolina Rabello de
authors.initials: AC
authors.lastname: Moraes
authors.forename: Karen Ristau
authors.initials: KR
authors.lastname: Sgambatti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mascarello
authors.forename: Louise Domeneghini
authors.initials: LD
authors.lastname: Chiaradia-Delatorre
authors.forename: Rosendo Augusto
authors.initials: RA
authors.lastname: Yunes
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Santos da Silva
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000097:blood* / Q000188:drug therapy; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C000625738:1-(2,5-dimethoxyphenyl)-3-(1-naphthyl)-2-propene-1-one; C494829:AIFM1 protein, human; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; C107489:BIRC5 protein, human; D047188:Chalcones; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D051028:bcl-2-Associated X Protein; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1