l-Amino acid oxidase isolated from calloselasma rhodostoma snake venom induces cytotoxicity and apoptosis in JAK2V617F-positive cell lines
Rev. bras. hematol. hemoter
;
38(2): 128-134, graf
Artículo
en Inglés
| LILACS
| ID: lil-787676
ABSTRACT
BACKGROUND:
Myeloproliferative neoplasms are Philadelphia chromosome-negative diseases characterized by hyperproliferation of mature myeloid cells, associated or not with the Janus kinase 2 tyrosine kinase mutation, JAK2V617F. As there is no curative therapy, researchers have been investigating new drugs to treat myeloproliferative neoplasms, including l-amino acid oxidase from Calloselasma rhodostoma snake venom (CR-LAAO), which is a toxin capable of eliciting apoptosis in several tumor cell lines.OBJECTIVE:
To evaluate the effects of l-amino acid oxidase from C. rhodostoma snake venom in the apoptotic machinery of JAK2-mutated cell lines.METHODS:
The HEL 92.1.7 and SET-2 cell lines were cultured with l-amino acid oxidase and catalase for 12 h at 37 °C in 5% carbon dioxide. The cell viability was assessed by the multi-table tournament method, the level of apoptosis was measured by flow cytometry, and the expression of cysteine-dependent aspartate-specific proteases and cleaved Poly(ADP-ribose) polymerase were analyzed by Western blotting.RESULTS:
l-Amino acid oxidase from C. rhodostoma snake venom was cytotoxic to HEL 92.1.7 and SET-2 cells (50% inhibitory concentration = 0.15 µg/mL and 1.5 µg/mL, respectively) and induced apoptosis in a concentration-dependent manner. Cell treatment with catalase mitigated the l-amino acid oxidase toxicity, indicating that hydrogen peroxide is a key component of its cytotoxic effect.The activated caspases 3 and 8 expression and cleaved PARP in HEL 92.1.7 and SET-2 cells confirmed the apoptosis activation by CR-LAAO.CONCLUSIONS:
l-Amino acid oxidase from C. rhodostoma snake venom is a potential antineoplastic agent against HEL 92.1.7 and SET-2 JAK2V617F-positive cells as it activates the extrinsic apoptosis pathway.
Texto completo:
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Índice:
LILACS (Américas)
Asunto principal:
Venenos de Serpiente
/
Betaína
/
Apoptosis
/
L-Aminoácido Oxidasa
/
Enfermedades Mielodisplásicas-Mieloproliferativas
/
Mutación
Límite:
Humanos
Idioma:
Inglés
Revista:
Rev. bras. hematol. hemoter
Asunto de la revista:
Hematología
Año:
2016
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
Brasil
/
Alemania
Institución/País de afiliación:
Universidade de São Paulo/BR
/
Universität Konstanz/DE
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