title: Synthesis and effects on cell viability of flavonols and 3-methyl ether derivatives on human leukemia cells.
abstract: Flavonoids are polyphenolic compounds which display an array of biological activities and are considered potential antitumor agents. Here we evaluated the antiproliferative activity of selected synthetic flavonoids against human leukemia cell lines. We found that 4'-bromoflavonol (flavonol 3) was the most potent. This compound inhibited proliferation in a concentration-dependent manner, induced apoptosis and blocked cell cycle progression at the S phase. Cell death was found to be associated with the cleavage and activation of multiple caspases, the activation of the mitogen-activated protein kinase pathway and the up-regulation of two death receptors (death receptor 4 and death receptor 5) for tumor necrosis factor-related apoptosis-inducing ligand. Moreover, combined treatments using 4'-bromoflavonol and TRAIL led to an increased cytotoxicity compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Canario de Investigación del Cáncer, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Burmistrova
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Canario de Investigación del Cáncer, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Marrero
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Canario de Investigación del Cáncer, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Estévez
authors.affiliation: Instituto Productos Naturales y Agrobiología, CSIC, Avenida Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Welsch
authors.affiliation: Instituto Productos Naturales y Agrobiología, CSIC, Avenida Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Brouard
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Canario de Investigación del Cáncer, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Quintana
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Canario de Investigación del Cáncer, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain. Electronic address: festevez@dbbf.ulpgc.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D044948:Flavonols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008738:Methyl Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D044948:Flavonols; D008738:Methyl Ethers
keywords: Apoptosis; Caspases; Cell cycle; Cytotoxicity; Death receptors; Flavonoids