4′-Hydroxychalcone Induces Ferroptosis in Glioblastoma Through the xCT/GSH/GPX4 Axis Under the Regulation of the AKT/mTORC1/4EBP1 Pathway

文献类型： 外文期刊

第一作者： Zhao, Renshuang

作者： Zhao, Renshuang;Yan, Yan;Li, Yaru;Yang, Xia;Liu, Yunyun;Li, Hongyang;Wu, Changzheng;Zhao, Zhehao;Li, Yiquan;Yan, Yan;Liu, Zirui;Li, Shanzhi

作者机构：

关键词： 4 '-hydroxychalcone; ferroptosis; glioblastoma; GPX4; mTORC1

期刊名称：PHYTOTHERAPY RESEARCH （ 影响因子：6.3； 五年影响因子：7.0 ）

ISSN： 0951-418X

年卷期： 2025 年

页码：

收录情况： SCI

摘要： Glioblastoma multiforme (GBM) is a common and malignant tumor in the field of neurosurgery. Natural chemotherapeutic agents are an appealing option due to their diverse activities and low cost. Ferroptosis, a form of programmed cell death, holds great potential for treating resistant cancers. The specific mechanism by which 4 '-hydroxychalcone extracted from Glycyrrhiza glabra L. induces glioma cell death remains unclear. This study aims to explore the molecular mechanism of 4 '-hydroxychalcone's effect on glioma cells. Through CCK-8 assay, cell scratch and invasion assay, q-PCR technology, WB detection and immunofluorescence, the inhibitory effect of 4 '-hydroxychalcone on glioma and its mechanism were analyzed. The study found that 20 mu M 4 '-hydroxychalcone could induce ferroptosis and inhibit the proliferation and epithelial-mesenchymal 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 vivo tumor model. Long-term animal toxicity experiments showed that high doses of 4 '-hydroxychalcone (100 mg/kg) did not cause damage to the organs of the animals. This study provides new insights into tumor ferroptosis research and traditional Chinese medicine-based treatment of GBM.

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