Evidence map›Paper›PMID 37108769›Full record

ArticleInternational journal of molecular sciences2023

MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer.

Bing Hu, Ru Chen, Ming Jiang, Situ Xiong, An Xie, Xiaoqiang Liu, Bin Fu

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. 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 · 2024
    Review
  8. Article
  9. Ferroptosis: An Emerging Target for Bladder Cancer Therapy.Current issues in molecular biology · 2023
    Review
  10. Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Bing HuDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
Ru ChenDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
Ming JiangDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
Situ XiongDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
An XieDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
Xiaoqiang LiuDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
Bin FuDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang 330006, China.
Nanchang University · CNFirst Affiliated Hospital of Nanchang University · CN

Funding

Jiangxi Provincial "Double Thousand Plan" Fund Project jxsq2019201027Key Project of Natural Science Foundation of Jiangxi Province 20212ACB206013
6 · The paper itself

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.

Indexed as

NF-E2-Related Factor 2Urinary Bladder NeoplasmsAntioxidantsGlutamate-Cysteine LigaseGlutathioneHumansKelch-Like ECH-Associated Protein 1Reactive Oxygen SpeciesAntioxidantsGCLM protein, humanGlutamate-Cysteine LigaseGlutathioneKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Reactive Oxygen Speciesbladder cancerGSH metabolismKeap1/NRF2/GCLMMTX-211proliferation

Identifiers

PMID37108769
PMCPMC10142351
OpenAlexW4366688041

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.