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

Autor(es):Mostrar menos -

Burin, Sandra Mara ^[1] ; Ghisla, Sandro ^[2] ; Ouchida, Amanda Tomie ^[3] ; Aissa, Alexandre Ferro ^[1] ; Berzoti Coelho, Maria Gabriela ^[1] ; Costa, Tassia Rafaella ^[1] ; Zambuzi Cardoso Marsola, Ana Paula ^[1] ; Pinto-Simoes, Belinda ^[4] ; Greggi Antunes, Lusania Maria ^[1] ; Curti, Carlos ^[5] ; Sampaio, Suely Vilela ^[1] ; de Castro, Fabiola Attie ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Konstanz, Dept Biol, Constance - Germany

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Internal Med, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14049 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 86, p. 309-320, MAY 2016.
• Citações Web of Science: 15

Resumo

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. (C) 2016 Published by Elsevier B.V. (AU)

• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático