MLN4924 Enhances RSL3-Induced Ferroptosis Sensitivity in Glioblastoma via Inhibiting the STAT3/GPX4 Axis

Clicks: 3
ID: 325419
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #43 of 48 articles by views in journal of carcinogenesis

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Glioblastoma (GBM) is one of the most aggressive and treatment-resistant tumors of the central nervous system, demanding innovative therapeutic strategies. Ferroptosis, an iron-driven lipid peroxidation-dependent cell death, has emerged as a potential means to overcome resistance, with glutathione peroxidase 4 (GPX4) as its key suppressor. MLN4924 (pevonedistat), a first-in-class inhibitor of neddylation currently in clinical trials, has shown strong antitumor activity across multiple malignancies. However, its role in ferroptosis regulation and the underlying molecular mechanisms remain poorly defined. Here, we show that MLN4924 induces ferroptosis, with GPX4 emerging as a central regulatory node. GPX4 expression is elevated in gliomas compared to normal brains, and its higher levels correlate with increased grades and worse patient prognosis. MLN4924 downregulates GPX4 mRNA by suppressing STAT3 signaling, whereas RSL3 directly inhibits GPX4 enzymatic activity. The combination of MLN4924 and RSL3 synergistically potentiates ferroptosis and, in vivo, suppresses subcutaneous tumor growth with a considerable biosafety. Collectively, these findings identify GPX4 as the principal mediator of MLN4924-induced ferroptosis and establish that dual targeting of GPX4 transcription and activity represents a promising therapeutic strategy for GBM.
Reference Key
openalex_W7203791037 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Zhou Jing, Fangyuan Wang, Hao Li, Bingqi Lu, Zian Li, Wulong Liang, X. M. Fu, Xinjun Wang
Journal journal of carcinogenesis
Year 2026
DOI
10.1093/carcin/bgag058
URL
https://doi.org/10.1093/carcin/bgag058
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.