title: Induction of G2/M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells.
abstract: Flavonoids are naturally occurring polyphenolic compounds which display a vast array of biological activities. In this study, we investigated the effects of tamarixetin on viability of human tumor cell lines and found that it was cytotoxic against leukemia cells and in particular P-glycoprotein-overexpressing K562/ADR cells. This compound inhibited proliferation in a concentration- and time-dependent manner, induced apoptosis and blocked cell cycle progression at G2 -M phase. This was associated with the accumulation of cyclin B1, Bub1 and p21(Cip1/Waf-1), changes in the phosphorylation status of cyclin B1, Cdk1, Cdc25C and MPM-2, and inhibition of tubulin polymerization. Moreover, cell death was found to be associated with cytochrome c release and cleavage of caspases and of poly(ADP-ribose) polymerase, and completely abrogated by the free-radical scavenger N-acetyl-L-cysteine. The sensitivity of leukemic cells to tamarixetin suggests that it should be considered for further preclinical and in vivo testing.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas de Gran Canaria, Spain.
authors.forename: Fabio
authors.initials: F
authors.lastname: Nicolini
authors.forename: Olga
authors.initials: O
authors.lastname: Burmistrova
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Marrero
authors.forename: Fernando
authors.initials: F
authors.lastname: Torres
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.forename: José
authors.initials: J
authors.lastname: Quintana
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004187:Disaccharides / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004187:Disaccharides; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; C508967:tamarixetin; D011794:Quercetin; D011065:Poly(ADP-ribose) Polymerases; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases
keywords: apoptosis; cell cycle arrest; flavonoids