Glutamic acid increased methotrexate polyglutamation and cytotoxicity in a CCRF-SB acute lymphoblastic leukemia cell line
Por:
Mendoza-Santiago, Alma, Becerra, Edgardo, Garay, Edith, Bah, Moustapha, Berumen-Segura, Laura, Escobar-Cabrera, Jesica, Hernandez-Perez, Abigail, Garcia-Alcocer, Guadalupe
Publicada:
1 ene 2019
Categoría:
Medicine (miscellaneous)
Resumen:
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 and Methods: 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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Filiaciones:
Mendoza-Santiago, Alma:
Unidad de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro, 76010, Mexico
Univ Autonoma Queretaro, Ctr Univ, Fac Quim, Unidad Invest Genet, Queretaro 76010, Mexico
Becerra, Edgardo:
Unidad de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro, 76010, Mexico
Univ Autonoma Queretaro, Ctr Univ, Fac Quim, Unidad Invest Genet, Queretaro 76010, Mexico
Garay, Edith:
Instituto de Neurobiología, Universidad Nacional Autónoma de México, México City, 04510, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Lab Invest Prod Nat, Queretaro 76010, Mexico
Bah, Moustapha:
Laboratorio de Investigación en Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Querétaro, 76010, Mexico
Univ Nacl Autonoma Mexico, Inst Neurobiol, Mexico City 04510, DF, Mexico
Berumen-Segura, Laura:
Unidad de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro, 76010, Mexico
Univ Autonoma Queretaro, Ctr Univ, Fac Quim, Unidad Invest Genet, Queretaro 76010, Mexico
Escobar-Cabrera, Jesica:
Unidad de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro, 76010, Mexico
Univ Autonoma Queretaro, Ctr Univ, Fac Quim, Unidad Invest Genet, Queretaro 76010, Mexico
Hernandez-Perez, Abigail:
Laboratorio de Investigación en Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Querétaro, 76010, Mexico
Univ Nacl Autonoma Mexico, Fac Quim, Lab Invest Prod Nat, Queretaro 76010, Mexico
Garcia-Alcocer, Guadalupe:
Unidad de Investigación Genética, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro, 76010, Mexico
Univ Autonoma Queretaro, Ctr Univ, Fac Quim, Unidad Invest Genet, Queretaro 76010, Mexico
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