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

详细信息    查看全文

• 作者：Sandra Mara Burin^a ; ^{sandra_burin@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author} ; Sandro Ghisla^b ; ^{Sandro.Ghisla@uni-konstanz.de" class="auth_mail" title="E-mail the corresponding author} ; Amanda Tomie Ouchida^c ; ^{amanda.tomie@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author} ; Alexandre Ferro Aissa^a ; ^{afaissa@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Maria Gabriela Berzoti Coelho^a ; ^{gabrielaberzoti@usp.br" class="auth_mail" title="E-mail the corresponding author} ; Tá ; ssia Rafaella Costa^a ; ^{tassiarc@fcfrp.usp.br" class="auth_mail" title="E-mail the corresponding author} ; Ana Paula Zambuzi Cardoso Marsola^a ; ^{anafarma_usp@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author} ; Belinda Pinto-Simõ ; es^d ; ^{bpsimoes@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Lusâ ; nia Maria Greggi Antunes^a ; ^{lusania@fcfrp.usp.br" class="auth_mail" title="E-mail the corresponding author} ; Carlos Curti^e ; ^{ccurti@usp.br" class="auth_mail" title="E-mail the corresponding author} ; Suely Vilela Sampaio^a ; ^{suvilela@usp.br" class="auth_mail" title="E-mail the corresponding author} ; Fabí ; ola Attié ; de Castro^a ; ^{castrofa@fcfrp.usp.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AC ; accelerated phase ; ANOVA ; analysis of variance ; AP ; advanced phase ; Bcr-Abl+ ; cell lines positive for the BCR-ABL1 oncogene ; CML ; chronic myeloid leukemia ; CML-AP ; chronic myeloid leukemia patients in the advanced phase of the disease ; CML-CP/T ; chronic myeloid leukemia patients in the chronic phase of the disease treated with imatinib mesylate ; CML-CP/WT ; chronic myeloid leukemia patients in the chronic phase of the disease without drug treatment ; CML-CP ; chronic myeloid leukemia patients i
• 刊名：International Journal of Biological Macromolecules
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：86
• 期：Complete
• 页码：309-320
• 全文大小：2832 K

文摘

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.