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

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2016
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Burin, Sandra Mara
Ouchida, Amanda Tomie
Aissa, Alexandre Ferro
Coelho, Maria Gabriela Berzoti
Costa, Tássia Rafaella
Marsola, Ana Paula Zambuzi Cardoso
Pinto-Simões, Belinda
Antunes, Lusânia Maria Greggi
de Castro, Fabíola Attié
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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.

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ISO 690BURIN, 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. 2016, 86, pp. 309-320. ISSN 0141-8130. eISSN 1879-0003. Available under: doi: 10.1016/j.ijbiomac.2016.01.069
BibTex
@article{Burin2016CRLAA-34275,
  year={2016},
  doi={10.1016/j.ijbiomac.2016.01.069},
  title={CR-LAAO antileukemic effect against Bcr-Abl+ cells is mediated by apoptosis and hydrogen peroxide},
  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}
}
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