当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES期刊下所有文献 > 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.

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.

journal_name

Int J Biol Macromol

journal_title

International journal of biological macromolecules

authors

Burin SM,Ghisla S,Ouchida AT,Aissa AF,Coelho MG,Costa TR,Marsola AP,Pinto-Simões B,Antunes LM,Curti C,Sampaio SV,de Castro FA

doi

10.1016/j.ijbiomac.2016.01.069

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

309-20

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(16)30070-8

journal_volume

86

pub_type

杂志文章

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