| Full text | |
| Author(s): Show less - |
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]
Total Authors: 12
|
| Affiliation: | [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
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | International Journal of Biological Macromolecules; v. 86, p. 309-320, MAY 2016. |
| Web of Science Citations: | 15 |
| Abstract | |
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) | |
| FAPESP's process: | 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis |
| Grantee: | Suely Vilela |
| Support Opportunities: | Research Projects - Thematic Grants |