Mechanism of leucovorin reversal of methotrexate cytotoxicity in human MCF-7 breast cancer cells
References (44)
Methotrexate therapy in rheumatoid arthritis: 15 Years experience
Am J Med
(1983)- et al.
Cyclosporine vs methotrexate for graft-vs-host disease prevention in patients given marrow grafts for leukemia: Long-term follow-up of three controlled trials
Blood
(1988) - et al.
Mechanism of inhibition of DHFR from bacterial and vertebrate sources by various classes of folate analogues
Biochim Biophys Acta
(1986) - et al.
The effect of methotrexate on intracellular folate pools in human MCF-7 breast cancer cells: Evidence for direct inhibition of purine synthesis
J Biol Chem
(1986) - et al.
Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate
J Biol Chem
(1987) - et al.
Identification and biochemical properties of 10-formyl dihydrofolate, a novel folate found in methotrexate-treated cells
J Biol Chem
(1988) - et al.
Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates
J Biol Chem
(1985) - et al.
Human thymidylate synthetase—III. Effects of methotrexate and folate analogs
Biochem Pharmacol
(1979) - et al.
Carrier mediated transport of the folic acid analogue, methotrexate, in the L1210 leukemia cell
J Biol Chem
(1968) - et al.
Influence of intracellular folates on methotrexate metabolism and cytotoxicity
Biochem Pharmacol
(1987)
Reversal of methotrexate binding to dihydrofolate reductase by dihydrofolate: Studies with pure enzyme and computer modeling network thermodynamics
J Biol Chem
Reactivation of dihydrofolate reduction inhibited by methotrexate or aminopterin
Arch Biochem Biophys
Direct experimental evidence for competitive inhibition of dihydrofolate reductase by methotrexate
Biochem Pharmacol
High pressure liquid chromatography: Separation and determination of rat liver folates
Arch Biochem Biophys
Mechanism of thymidylate synthase inhibition by methotrexate in human neoplastic cell lines and normal human myeloid progenitor cells
J Biol Chem
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
Anal Biochem
Methotrexate for psoriasis
Arch Dermatol
Intrinsic resistance to methotrexate of cultured mammalian cells in relation to the inhibition kinetics of their dihydrofolate reductase
Cancer Res
Interaction of polyglutamyl derivatives of MTX, 10-deazaaminopterin, and di-hydrofolate with dihydrofolate reductase
Cancer Res
Effect of methotrexate on intracellular folate pools in purified myeloid precursor cells from normal human bone marrow
J Clin Invest
The effects of 4-amino-antifolates on 5- formyltetrahydrofolate metabolism in L1210 cells
J Biol Chem
Cited by (22)
Supramolecular encapsulation of nanocrystalline Schiff bases into β-cyclodextrin for multifold enrichment of bio-potency
2022, Carbohydrate PolymersCitation Excerpt :In brief, MCF-7 cells were seeded in 24-well culture plates (105 cells/well) in a complete medium. After 24 h, MCF-7 cells were treated with four best doses (10 μM, 20 μM, 40 μM, 80 μM), DMSO as vehicle control, and methotrexate (10 μM) as the positive control (Boarman, Baram, & Allegra, 1990); for time-dependent experiments, cells were treated with specific concentrations of crude extract in fresh medium for 24 and 48 h. After treatments, cells were harvested by chilled PBS, fixed for 5 min at −20 °C in methanol, then washed and re-suspended in 1 mL PBS buffer.
Folinic acid rescue during methotrexate treatment for low-risk gestational trophoblastic neoplasia – How much is just right?
2021, Gynecologic OncologyCitation Excerpt :FA may either aid or hinder chemotherapy. Since FA competes with MTX in its action on dihydrofolate reductase, its use may limit toxicity and allow treatment to be continued, alternatively, excessive FA may prevent the inhibition of dihydrofolate reductase and might decrease the efficacy of MTX and decrease the remission rate or increase the occurrence of relapse, as described in cases of lymphoblastic leukemia and non-Hodgkin lymphoma [13–15]. Additionally, FA may increase the overall cost of therapy.
Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder
2020, Seminars in Pediatric NeurologyCitation Excerpt :The improvement in an important symptom associated with ASD, irritability, suggests that d,l-leucovorin may be an alternative to antipsychotic drugs, which have significant short- and long-term AEs in children. Additionally, d,l-leucovorin can normalize folate-dependent one-carbon metabolism by readily entering the folate cycle without being reduced by dihydrofolate reductase (DHFR in Fig. 1).83 Early studies on CFD and ASD demonstrated a strong positive effect of d,l-leucovorin in young children with ASD on both neurologic and cognitive development.22
Challenging the clinical relevance of folinic acid over rescue after high dose methotrexate (HDMTX)
2013, Medical HypothesesCitation Excerpt :When the dose of MTX was doubled, the dose of FA needed to maintain the increased life span and avoid toxic deaths rose by 3.3-fold in the leukemia group (to 400 mg/kg) and 4-fold in the sarcoma group (to 288 mg/kg). Pinedo [14] and Boarman [15] Koizumi [16] reported similar findings. Bertino [11], noted that, “If LV administration is delayed for more than 42 or 48 h following HD MTX, severe and irreversible toxicity may occur”.
Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation
2006, Biochemical PharmacologyCitation Excerpt :In the cell, excess leucovorin is rapidly converted to 5,10-methenyl-THF and then to 5,10-methylene-THF [32]. Alterations in intracellular reduced folate pools in response to leucovorin supplementation are one of the mechanisms of rescue from MTX toxicity [10,33,34]. On the other side, elevation of intracellular 5,10-methylene-THF is the basis for the application of leucovorin in combination with 5-fluorouracil, an inhibitor of thymidylate synthase, in cancer chemotherapy.
Leucovorin rescue of human cancer and bone marrow cells following edatrexate or methotrexate
1994, Biochemical Pharmacology