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The specific mechanism by which 4\u2032\u2010hydroxychalcone extracted from <jats:styled-content style=\"fixed-case\"><jats:italic>Glycyrrhiza glabra<\/jats:italic><\/jats:styled-content> L. induces glioma cell death remains unclear. This study aims to explore the molecular mechanism of 4\u2032\u2010hydroxychalcone's effect on glioma cells. Through CCK\u20108 assay, cell scratch and invasion assay, q\u2010PCR technology, WB detection and immunofluorescence, the inhibitory effect of 4\u2032\u2010hydroxychalcone on glioma and its mechanism were analyzed. The study found that 20\u2009\u03bcM 4\u2032\u2010hydroxychalcone could induce ferroptosis and inhibit the proliferation and epithelial\u2010mesenchymal transition of glioma cells. Subsequent analysis revealed that this process of ferroptosis was triggered through the xCT\/GSH\/GPX4 axis, which was regulated by the AKT\/mTORC1\/4EBP1 pathway. Similar tumor inhibitory effects to the clinical drug temozolomide were also observed in the in\u00a0vivo tumor model. Long\u2010term animal toxicity experiments showed that high doses of 4\u2032\u2010hydroxychalcone (100\u2009mg\/kg) did not cause damage to the organs of the animals. This study provides new insights into tumor ferroptosis research and traditional Chinese medicine\u2010based treatment of GBM.<\/jats:p>","DOI":"10.1002\/ptr.70004","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T03:27:52Z","timestamp":1756178872000},"page":"4348-4365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["4\u2032\u2010Hydroxychalcone Induces Ferroptosis in Glioblastoma Through the <scp>xCT<\/scp>\/<scp>GSH<\/scp>\/<scp>GPX4<\/scp> Axis Under the Regulation of the <scp>AKT<\/scp>\/<scp>mTORC1<\/scp>\/<scp>4EBP1<\/scp> Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Renshuang","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Animal Science Zhejiang University  Hangzhou People's Republic of 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