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CR-LAAO antileukemic effect against Bcr-Abl+ cells is mediated by apoptosis and hydrogen peroxide

CR-LAAO antileukemic effect against Bcr-Abl+ cells is mediated by apoptosis and hydrogen peroxide

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BURIN, Sandra Mara, Sandro GHISLA, Amanda Tomie OUCHIDA, Alexandre Ferro AISSA, Maria Gabriela Berzoti COELHO, Tássia Rafaella COSTA, Ana Paula Zambuzi Cardoso MARSOLA, Belinda PINTO-SIMÕES, Lusânia Maria Greggi ANTUNES, Fabíola Attié DE CASTRO, 2016. CR-LAAO antileukemic effect against Bcr-Abl+ cells is mediated by apoptosis and hydrogen peroxide. In: International Journal of Biological Macromolecules. 86, pp. 309-320. ISSN 0141-8130. eISSN 1879-0003. Available under: doi: 10.1016/j.ijbiomac.2016.01.069

@article{Burin2016CRLAA-34275, title={CR-LAAO antileukemic effect against Bcr-Abl+ cells is mediated by apoptosis and hydrogen peroxide}, year={2016}, doi={10.1016/j.ijbiomac.2016.01.069}, volume={86}, issn={0141-8130}, journal={International Journal of Biological Macromolecules}, pages={309--320}, author={Burin, Sandra Mara and Ghisla, Sandro and Ouchida, Amanda Tomie and Aissa, Alexandre Ferro and Coelho, Maria Gabriela Berzoti and Costa, Tássia Rafaella and Marsola, Ana Paula Zambuzi Cardoso and Pinto-Simões, Belinda and Antunes, Lusânia Maria Greggi and de Castro, Fabíola Attié} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/34275"> <dc:contributor>Ghisla, Sandro</dc:contributor> <dc:contributor>Pinto-Simões, Belinda</dc:contributor> <dc:creator>Coelho, Maria Gabriela Berzoti</dc:creator> <dc:creator>Costa, Tássia Rafaella</dc:creator> <dc:creator>Marsola, Ana Paula Zambuzi Cardoso</dc:creator> <dc:contributor>Burin, Sandra Mara</dc:contributor> <dc:contributor>de Castro, Fabíola Attié</dc:contributor> <dc:creator>Antunes, Lusânia Maria Greggi</dc:creator> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:title>CR-LAAO antileukemic effect against Bcr-Abl+ cells is mediated by apoptosis and hydrogen peroxide</dcterms:title> <dc:creator>Ouchida, Amanda Tomie</dc:creator> <dc:contributor>Ouchida, Amanda Tomie</dc:contributor> <dc:contributor>Coelho, Maria Gabriela Berzoti</dc:contributor> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Marsola, Ana Paula Zambuzi Cardoso</dc:contributor> <dc:contributor>Aissa, Alexandre Ferro</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/34275"/> <dc:creator>Pinto-Simões, Belinda</dc:creator> <dc:creator>Ghisla, Sandro</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:language>eng</dc:language> <dc:creator>de Castro, Fabíola Attié</dc:creator> <dc:creator>Aissa, Alexandre Ferro</dc:creator> <dc:creator>Burin, Sandra Mara</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-06-08T08:35:16Z</dc:date> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-06-08T08:35:16Z</dcterms:available> <dcterms:abstract xml:lang="eng">Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Bcr-Abl tyrosine kinase protein, which confers resistance to apoptosis in leukemic cells. Tyrosine kinase inhibitors (TKIs) are effectively used to treat CML; however, CML patients in the advanced (CML-AP) and chronic (CML-CP) phases of the disease are usually resistant to TKI therapy. Thus, it is necessary to seek for novel agents to treat CML, such as the enzyme l-amino acid oxidase from Calloselasma rhodostoma (CR-LAAO) snake venom. We examined the antitumor effect of CR-LAAO in Bcr-Abl(+) cell lines and peripheral blood mononuclear cells (PBMC) from healthy subjects and CML patients. CR-LAAO was more cytotoxic towards Bcr-Abl(+) cell lines than towards healthy subjects' PBMC. The H2O2 produced during the enzymatic action of CR-LAAO mediated its cytotoxic effect. The CR-LAAO induced apoptosis in Bcr-Abl(+) cells, as detected by caspases 3, 8, and 9 activation, loss of mitochondrial membrane potential, and DNA damage. CR-LAAO elicited apoptosis in PBMC from CML-CP patients without TKI treatment more strongly than in PBMC from healthy subjects and TKI-treated CML-CP and CML-AP patients. The antitumor effect of CR-LAAO against Bcr-Abl(+) cells makes this toxin a promising candidate to CML therapy.</dcterms:abstract> <dc:contributor>Costa, Tássia Rafaella</dc:contributor> <dcterms:issued>2016</dcterms:issued> <dc:contributor>Antunes, Lusânia Maria Greggi</dc:contributor> </rdf:Description> </rdf:RDF>

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