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Updated: Jun 26, 2026
Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
Cryptotanshinone Targets Ferroptosis in Glioma via the EGFR/ROS Signaling Pathway
Jiazheng Hu1, Xinxin Liang2, Yongshi Liao3
1Department of Neurosurgery, The Seventh Affiliated Hospital, Hengyang Medical School, University of South China, Changsha, 410006, Hunan, China.
Abstract:
To investigate the regulatory effects of cryptotanshinone (CTS) on the biological behavior of glioma cells and its underlying molecular mechanisms, with a particular focus on the role of the epidermal growth factor receptor/reactive oxygen species (EGFR/ROS) pathway in ferroptosis-mediated antitumor activity. Glioma cell behaviors were monitored through Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays. Intracellular and tumor tissue levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ferrous iron (Fe²⁺), glutathione/glutathione disulfide (GSH/GSSG) ratio, and malondialdehyde (MDA) were assessed. Glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), acyl-CoA synthetase long-chain family member 4 (ACSL4), epidermal growth factor receptor (EGFR), and Ki67 expression was examined using western blotting and immunohistochemistry. Network pharmacology and molecular docking were employed to predict potential cryptotanshinone targets. An in vivo glioma model was created by implanting tumor cells into nude mice. CTS inhibited glioma cell malignant phenotype, while promoting ROS accumulation, MMP loss, Fe²⁺ elevation, and GSH depletion. CTS also modulated ferroptosis-associated molecules, characterized by downregulation of GPX4 and SLC7A11 and upregulation of ACSL4. EGFR was identified as a central target, which was experimentally validated to mediate the antitumor and ferroptosis-inducing effects of CTS. In vivo, CTS suppressed tumor growth and activated ferroptosis, whereas EGFR overexpression partially reversed these protective effects. CTS induces ferroptosis in glioma cells by inhibiting EGFR and enhancing ROS signaling, thereby suppressing tumor proliferation and invasion.
Insights
Cryptotanshinone (CTS) inhibits glioma cell growth by inducing ferroptosis, a cell death process. This occurs by suppressing the epidermal growth factor receptor (EGFR) and boosting reactive oxygen species (ROS) signaling, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Glioma is an aggressive brain tumor with limited treatment options.
- Ferroptosis, a regulated form of cell death, presents a promising avenue for cancer therapy.
- The role of the epidermal growth factor receptor (EGFR)/reactive oxygen species (ROS) pathway in cryptotanshinone (CTS)-induced ferroptosis in glioma remains unclear.
Purpose of the Study:
- To investigate the regulatory effects of cryptotanshinone (CTS) on glioma cell behavior.
- To elucidate the underlying molecular mechanisms, focusing on the EGFR/ROS pathway in ferroptosis-mediated antitumor activity.
- To evaluate the therapeutic potential of CTS in an in vivo glioma model.
Main Methods:
- In vitro assays (CCK-8, colony formation, wound healing, Transwell) assessed glioma cell behavior.
- Biochemical assays measured ROS, mitochondrial membrane potential (MMP), ferrous iron (Fe²⁺), glutathione (GSH), and malondialdehyde (MDA) levels.
- Western blotting and immunohistochemistry analyzed key proteins (GPX4, SLC7A11, ACSL4, EGFR, Ki67); network pharmacology and molecular docking predicted CTS targets; an in vivo glioma model was used for further validation.
Main Results:
- CTS inhibited glioma cell proliferation and invasion, inducing ferroptosis characterized by increased ROS, MMP loss, elevated Fe²⁺, and GSH depletion.
- CTS modulated ferroptosis markers, downregulating GPX4 and SLC7A11 while upregulating ACSL4.
- EGFR was identified as a key target; CTS inhibited EGFR, suppressed tumor growth, and activated ferroptosis in vivo, with EGFR overexpression partially reversing these effects.
Conclusions:
- Cryptotanshinone (CTS) effectively suppresses glioma progression by inducing ferroptosis.
- The mechanism involves the inhibition of the EGFR pathway and the enhancement of ROS signaling.
- CTS demonstrates significant potential as an antitumor agent for glioma treatment.
