ArticleInternational journal of molecular sciences2023
MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Long noncoding RNA PCAT7 confers radioresistance of esophageal squamous cell carcinoma by promoting GCLM-mediated anti-ferroptosis.Journal of translational medicine · 2026Article
- The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation.Cell biochemistry and biophysics · 2025Review
- Ferroptosis as a therapeutic target in glioblastoma: Mechanisms and emerging strategies.Molecular therapy. Nucleic acids · 2025Review
- ABCG2 Mediates Resistance to the Dual EGFR and PI3K Inhibitor MTX-211 in Cancer Cells.International journal of molecular sciences · 2024Article
- Nuclear factor erythroid 2-related factor 2 promotes radioresistance by regulating glutamate-cysteine ligase modifier subunit and its unique immunoinvasive pattern.Biomolecules & biomedicine · 2024Article
- Molecular mechanisms of ferroptosis and its effects on bladder cancer.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- Elucidation of the mechanism of berberine against gastric mucosa injury in a rat model with chronic atrophic gastritis based on a combined strategy of multi-omics and molecular biology.Frontiers in pharmacology · 2024Article
- Ferroptosis: An Emerging Target for Bladder Cancer Therapy.Current issues in molecular biology · 2023Review
- Regulation of iron metabolism and ferroptosis in cancer stem cells.Frontiers in oncology · 2023Review
- Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Globally, bladder cancer (BLCA) is still the leading cause of death in patients with tumors. The function and underlying mechanism of MTX-211, an EFGR and PI3K kinase inhibitor, have not been elucidated. This study examined the function of MTX-211 in BLCA cells using in vitro and in vivo assays. RNA sequencing, quantitative real-time polymerase chain reaction, Western blotting, co-immunoprecipitation, and immunofluorescence were performed to elucidate the underlying mechanism. Our observations revealed that MTX-211 has a time- and concentration-dependent inhibitory effect on bladder cancer cell proliferation. Flow cytometry analysis showed that cell apoptosis and G0/G1 cell cycle arrest were significantly induced by MTX-211. MTX-211 inhibited intracellular glutathione (GSH) metabolism, leading to a decrease in GSH levels and an increase in reactive oxygen species. GSH supplementation partly reversed the inhibitory effects of MTX-211. Further experiments verified that MTX-211 promoted NFR2 protein ubiquitinated degradation via facilitating the binding of Keap1 and NRF2, subsequently resulting in the downregulated expression of GCLM, which plays a vital role in GSH synthesis. This study provided evidence that MTX-211 effectively inhibited BLCA cell proliferation via depleting GSH levels through Keap1/NRF2/GCLM signaling pathway. Thus, MTX-211 could be a promising therapeutic agent for cancer.
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Registered trials
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