ArticleBritish journal of cancer2013
γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 29 citations in OpenAlex.
- Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy.Cancers · 2026Review
- Tolypothrix Dichloromethane Ethylacetate fraction (TDEF) inhibits cisplatin resistance H357 cell through PI3K/AKT/beta-catenin pathway.American journal of cancer research · 2024Article
- A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.Life science alliance · 2023Article
- Up-regulation of ABCG1 is associated with methotrexate resistance in acute lymphoblastic leukemia cells.Frontiers in pharmacology · 2023Article
- Interaction between glycolysis‒cholesterol synthesis axis and tumor microenvironment reveal that gamma-glutamyl hydrolase suppresses glycolysis in colon cancer.Frontiers in immunology · 2022Article
- pH assists simultaneous determination of folic acid and vitamin DRSC advances · 2021Article
- Identification of genes involved in inbreeding depression of reproduction in Langshan chickens.Animal bioscience · 2021Article
- Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma.Frontiers in genetics · 2021Article
- Enzymes involved in folate metabolism and its implication for cancer treatment.Nutrition research and practice · 2020Review
- High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-1.Journal of cancer research and clinical oncology · 2020Article
- Article
- Deregulation of folate pathway gene expression correlates with poor prognosis in acute leukemia.Oncology letters · 2019Article
- Coenzyme FJournal of bacteriology · 2018Article
- High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer.International journal of molecular sciences · 2017Article
- Serum protein gamma-glutamyl hydrolase, Ig gamma-3 chain C region, and haptoglobin are associated with the syndromes of pulmonary tuberculosis in traditional Chinese medicine.BMC complementary and alternative medicine · 2015Article
- γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.Genes & nutrition · 2015Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundγ-Glutamyl hydrolase (GGH) regulates intracellular folate and antifolates for optimal nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. The modulation of GGH may therefore affect chemosensitivity of cancer cells, and exogenous folate levels may further modify this effect.
methodsWe generated a novel model of GGH modulation in human HCT116 and MDA-MB-435 cancer cells and investigated the effect of GGH modulation on chemosensitivity to 5-fluorouracil (5FU) and methotrexate (MTX) at different folate concentrations in vitro and in vivo.
resultsOverexpression of GGH significantly decreased chemosensitivity of MDA-MB-435 cells to 5FU and MTX at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect was observed only at very high folate concentration, and as the folate concentration decreased this effect became null or paradoxically increased. This in vitro observation was confirmed in vivo. Inhibition of GGH significantly increased chemosensitivity of both cancer cells to 5FU at all folate concentrations. Unexpectedly, GGH inhibition significantly decreased chemosensitivity of both cancer cells to MTX at all folate concentrations. In both GGH modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increased as folate concentration increased.
conclusionModulation of GGH affects chemosensitivity of cancer cells to 5FU and MTX, and exogenous folate levels can further modify the effects.
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