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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Zebularine induces chemosensitization to methotrexate and efficiently decreases AhR gene methylation in childhood acute lymphoblastic leukemia cells

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Autor(es):
Andrade, Augusto F. [1] ; Borges, Kleiton S. [1] ; Castro-Gamero, Angel M. [1] ; Silveira, Vanessa S. [2] ; Suazo, Veridiana K. [2] ; Oliveira, Jaqueline C. [1] ; Moreno, Daniel A. [1] ; de Paula Queiroz, Rosane G. [2] ; Scrideli, Carlos A. [2] ; Tone, Luiz G. [2, 1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14048900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, BR-14048900 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: ANTI-CANCER DRUGS; v. 25, n. 1, p. 72-81, JAN 2014.
Citações Web of Science: 15
Resumo

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in childhood. Despite the advances in treatment, about 20% of patients relapse and/or die, indicating the need for different therapies for this group. Zebularine (ZB) is a potent DNA methyltransferase (DNMT) inhibitor and has been associated with gene demethylation and enhancement of tumor chemosensitivity. This study aimed to evaluate the effects of ZB, alone or combined with chemotherapeutics (methotrexate and vincristine), on childhood ALL cell lines. Cell proliferation, apoptosis, and clonogenic capacity were studied in Jurkat and ReH cell lines. Bisulfite modification, followed by methylation-specific PCR was carried out to evaluate aryl hydrocarbon receptor (AhR) methylation status. Gene expression of DNMT1, DNMT3a, DNMT3b, and AhR was assessed using qRT-PCR. Both cell cultures were sensitive to ZB, showing a dose-dependent and time-dependent response (P<0.05). ZB induced apoptosis and decreased clonogenic capacity in both cell lines. Combination with methotrexate resulted in a strong synergistic effect, whereas combination with vincristine led to an antagonistic response in both cell lines. ZB treatment decreased gene expression of the three DNMTs and induced AhR gene promoter demethylation and its re-expression. These results indicate that ZB may be a promising drug for the adjuvant treatment of ALL, mainly when combined with methotrexate. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams \& Wilkins. (AU)

Processo FAPESP: 10/14378-7 - Avaliação dos efeitos antineoplásicos da zebularina em linhagens pediátricas de leucemia linfóide aguda
Beneficiário:Augusto Faria Andrade
Linha de fomento: Bolsas no Brasil - Mestrado