title: Effect of nitric oxide on the daunorubicin efflux mechanism in K562 cells.
abstract: NO (nitric oxide) donating drugs have been investigated for their important role in the sensitization of neoplastic cells to chemotherapy drugs. The goal of this work was to investigate the involvement of NO in the resistance of K562 cells to DNR (daunorubicin). Only simultaneous addition of DNR and SNAP (S-nitroso-N-acetyl-dl-penicillamine) caused significant cell death by apoptosis. Combination of the compounds decreased Bcl-2 and survivin, and increased Bax and active-caspase 3 expression. Fluorescence microscope and cytometric analysis showed that DNR and SNAP together caused DNR intracellular accumulation in K562 cells. RT-PCR (reverse transcription-PCR) analysis showed that DNR and SNAP, alone or in association, produced significant decreases in lrp expression. abcc1 gene expression was unaffected by the presence of SNAP, but when treated with DNR there was a small reduction that was intensified by DNR and SNAP in combination. The transport mechanism involved in the resistance to DNR in K562 cells involves ABCC1 and LRP (lung resistance protein) resistance proteins. DNR and SNAP inhibition of the expression of these proteins occurs by distinct mechanisms, and this disrupts the K562 resistance to DNR.
authors.affiliation: Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Campus Trindade, CEP: 88040-900, Florianpolis, SC, Brazil.
authors.forename: Juliana Costa
authors.initials: JC
authors.lastname: Curta
authors.forename: Ana Carolina Rabello
authors.initials: AC
authors.lastname: de Moraes
authors.forename: Marley Aparecida
authors.initials: MA
authors.lastname: Licínio
authors.forename: Aline
authors.initials: A
authors.lastname: Costa
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Santos-Silva
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000378:metabolism* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D003630:Daunorubicin; D051034:Inhibitor of Apoptosis Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D019253:Proto-Oncogene Proteins c-bcl-2; D026423:S-Nitroso-N-Acetylpenicillamine; D000077022:Survivin; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C107489:BIRC5 protein, human; C475476:LRP1 protein, human; C505407:CASP3 protein, human; C421109:multidrug resistance-associated protein 1