Glutamic Acid Increased Methotrexate Polyglutamation and Cytotoxicity in a CCRF-SB Acute Lymphoblastic Leukemia Cell Line.
Medicina (Kaunas)
; 55(12)2019 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-31779260
ABSTRACT
Background and Objectives:
Acute lymphoblastic leukemia (ALL) is the most common type of cancer in childhood. The majority of patients respond to treatment, but those with resistant phenotypes suffer relapse or death. The antifolate methotrexate (MTX) is the most commonly used drug against ALL due to its efficacy. Once inside leukemic cells, MTX is metabolized into methotrexate polyglutamates (MTX-PG) by action of the enzyme folylpolyglutamate synthetase (FPGS), leading to a longer action compared to that of MTX alone. Materials andMethods:
In this work, we demonstrated that the combination treatment of methotrexate and 5 and 10 mM glutamic acid could enhance methotrexate cytotoxicity in CCRF-SB (B-ALL) cells. In addition, MTX plus 20 mM glutamic acid was able to improve the synthesis of MTX-PG5.Results:
All treatments induced an increase in FPGS expression compared to that of the control group. Furthermore, we detected different cellular expression patterns of FPGS in the different treatments.Conclusion:
Based on these findings, we demonstrated that levels of methotrexate polyglutamates (MTX-PGs) could be a key determinant of methotrexate-induced cytotoxicity in CCRF-SB acute lymphoblastic leukemia cells.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ácido Poliglutâmico
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Protocolos de Quimioterapia Combinada Antineoplásica
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Metotrexato
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Ácido Glutâmico
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Linhagem Celular Tumoral
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Antineoplásicos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article