Glutamic Acid Increased Methotrexate Polyglutamation and Cytotoxicity in a CCRF-SB Acute Lymphoblastic Leukemia Cell Line

: 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 insi...

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Published in:Medicina (Kaunas, Lithuania) Lithuania), 2019-11, Vol.55 (12), p.758
Main Authors: Mendoza-Santiago, Alma, Becerra, Edgardo, Garay, Edith, Bah, Moustapha, Berumen-Segura, Laura, Escobar-Cabrera, Jesica, Hernández-Pérez, Abigail, García-Alcocer, Guadalupe
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Antineoplastic Combined Chemotherapy Protocols
Cell Line
Cell Line, Tumor - drug effects
Glutamic Acid - pharmacology
Humans
Methotrexate - analogs & derivatives
Methotrexate - pharmacology
Polyglutamic Acid - analogs & derivatives
Polyglutamic Acid - pharmacology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
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Summary:: 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. 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-PG . 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. : 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.
ISSN:1648-9144
1010-660X
1648-9144
DOI:10.3390/medicina55120758