ArticleFrontiers in oncology2021
Studies of Glyoxalase 1-Linked Multidrug Resistance Reveal Glycolysis-Derived Reactive Metabolite, Methylglyoxal, Is a Common Contributor in Cancer Chemotherapy Targeting the Spliceosome.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Evaluation of Darifenacin for T-Cell Acute Lymphoblastic Leukemia: Selective Targeting of the Non-Neuronal Cholinergic System and Lysosomal Cathepsins.International journal of molecular sciences · 2026Article
- A Chemical Mechanistic Path Leads the Way to Cellular Argpyrimidine.Journal of the American Chemical Society · 2025Article
- Gender-Dependent Cognitive and Metabolic Benefits Due to Glyoxalase 1 (Glo1) Overexpression in Age-Accelerated SAMP8 Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Increased antioxidative defense and reduced advanced glycation end-product formation by metabolic adaptation in non-small-cell-lung-cancer patients.Nature communications · 2025Article
- Mapping the Landscape of Anti-Breast Cancer Drug Discovery in Saudi Arabia: A Bibliometric Analysis (2019-2023).Scientifica · 2025Article
- Metformin in gynecological disorders: pathogenic insights and therapeutic implications.Frontiers in pharmacology · 2025Review
- Simplified and economic measurement of glyoxalase I activity using 2,4-dinitrophenylhydrazine: A valuable tool for researchers.Biology methods & protocols · 2025Article
- Glyoxalase 1 gene expression in various types of cancer cells immunopathology: a pan-cancer analysis study.Frontiers in oncology · 2025Article
- Dual roles of methylglyoxal in cancer.Frontiers in oncology · 2025Review
- Cytotoxic, anti-inflammatory, antioxidant, and anti-glyoxalase-I evaluation of chelating substances: In silico and in vitro study.PloS one · 2025Article
- Article
- Glyoxalase 1: Emerging biomarker and therapeutic target in cervical cancer progression.PloS one · 2024Article
- The PKM2 inhibitor shikonin enhances piceatannol-induced apoptosis of glyoxalase I-dependent cancer cells.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Leveraging histone glycation for cancer diagnostics and therapeutics.Trends in cancer · 2023Review
- Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers.Acta pharmaceutica Sinica. B · 2023Review
- The Glycolysis-derived α-Dicarbonyl Metabolite Methylglyoxal is a UVA-photosensitizer Causing the Photooxidative Elimination of HaCaT Keratinocytes with Induction of Oxidative and Proteotoxic Stress Response Gene ExpressionPhotochemistry and photobiology · 2023Article
- Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells.Molecules and cells · 2022Review
- An Introduction to the Special Issue "Protein Glycation in Food, Nutrition, Health and Disease".International journal of molecular sciences · 2022Article
- Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress.International journal of molecular sciences · 2022Article
- Emerging Glycation-Based Therapeutics-Glyoxalase 1 Inducers and Glyoxalase 1 Inhibitors.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor glycolysis is a target for cancer chemotherapy. Methylglyoxal (MG) is a reactive metabolite formed mainly as a by-product in anaerobic glycolysis, metabolized by glyoxalase 1 (Glo1) of the glyoxalase system. We investigated the role of MG and Glo1 in cancer chemotherapy related in multidrug resistance (MDR).
methodsHuman Glo1 was overexpressed in HEK293 cells and the effect on anticancer drug potency, drug-induced increase in MG and mechanism of cytotoxicity characterized. Drug-induced increased MG and the mechanisms driving it were investigated and the proteomic response to MG-induced cytotoxicity explored by high mass resolution proteomics of cytoplasmic and other subcellular protein extracts. Glo1 expression data of 1,040 human tumor cell lines and 7,489 tumors were examined for functional correlates and impact of cancer patient survival.
resultsOverexpression of Glo1 decreased cytotoxicity of antitumor drugs, impairing antiproliferative activity of alkylating agents, topoisomerase inhibitors, antitubulins, and antimetabolites. Antitumor drugs increased MG to cytotoxic levels which contributed to the cytotoxic, antiproliferative mechanism of action, consistent with Glo1-mediated MDR. This was linked to off-target effects of drugs on glycolysis and was potentiated in hypoxia. MG activated the intrinsic pathway of apoptosis, with decrease of mitochondrial and spliceosomal proteins. Spliceosomal proteins were targets of MG modification. Spliceosomal gene expression correlated positively with Glo1 in human tumor cell lines and tumors. In clinical chemotherapy of breast cancer, increased expression of Glo1 was associated with decreased patient survival, with hazard ratio (HR) = 1.82 (logrank
conclusionsWe conclude that MG-mediated cytotoxicity contributes to the cancer chemotherapeutic response and targets the spliceosome. High expression of Glo1 contributes to multidrug resistance by shielding the spliceosome from MG modification and decreasing survival in the chemotherapy of breast cancer. Adjunct chemotherapy with Glo1 inhibitor may improve treatment outcomes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.