title: Astragalin heptaacetate-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway.
abstract: Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. Here we demonstrate that the flavonoid derivative astragalin heptaacetate (AHA) induces cell death. This was prevented by the non-specific caspase inhibitors z-VAD-fmk and Q-VD-OPH, and reduced by the selective caspase-4 inhibitor z-LEVD-fmk. AHA-induced cell death was found to be: (i) associated with the release of cytochrome c, (ii) suppressed by the overexpression of Bcl-x(L), (iii) amplified by inhibition of extracellular signal-regulated kinases (ERKs) 1/2 and c-jun NH(2)-terminal kinases/stress activated protein kinases (JNK/SAPK) signaling, and (iv) completely abrogated by the free-radical scavenger N-acetyl-l-cysteine.
authors.affiliation: Departamento de Bioquímica, Unidad Asociada al Consejo Superior de Investigaciones Científicas, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigación del Cáncer, Plaza Dr. Pasteur s/n, Las Palmas de Gran Canaria, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Burmistrova
authors.forename: José
authors.initials: J
authors.lastname: Quintana
authors.forename: Jesús G
authors.initials: JG
authors.lastname: Díaz
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D007938:Leukemia / Q000201:enzymology / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D006027:Glycosides; D044949:Kaempferols; D019253:Proto-Oncogene Proteins c-bcl-2; D011804:Quinolines; C562213:astragalin heptaacetate; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C468548:quinoline-val-asp(OMe)-CH2-OPH; D045304:Cytochromes c; D020169:Caspases