ATF3 Promotes Solasonine-Triggered Ferroptosis in Glioma Cells by Suppressing Glycolysis.
- 1Blood Transfusion Department, The Second Hospital of Jilin University, Changchun, China.
- 2Department of Laboratory, The Second Hospital of Jilin University, Changchun, China.
- 3Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.
Abstract
Background
Glioma cells are characterized by rapid proliferation, a high degree of invasiveness, and significant heterogeneity. Despite the application of various treatment regimens in recent years, the prognosis for glioma remains poor. The induction of ferroptosis in tumor cells has emerged as a promising therapeutic approach. Solasonine (SS), a steroidal alkaloid derived from plants of the Solanaceae family, has multiple antitumor effects. However, whether it can inhibit glioma growth and its mechanism of action have not been studied.Methods
The effects of SS on ferroptosis in glioma cells were analyzed by detecting the levels of ferrous ions, reactive oxygen species, and malondialdehyde. The role of activating transcription factor 3 (ATF3) in SS-induced ferroptosis in glioma cells was analyzed using western blotting, immunofluorescence, and confocal microscopy. An in vivo mouse model of glioma was constructed to further investigate the effects of SS.Results
We found that SS inhibited the proliferation of glioma cells and promoted their ferroptosis. SS treatment increased the intracellular ferrous ion, malondialdehyde, and reactive oxygen species levels. It increased the intracellular hydrogen peroxide level by regulating ATF3 to inhibit glycolysis and suppress the antioxidant system. Increased hydrogen peroxide levels activated nuclear receptor coactivator 4-dependent ferritinophagy and increased intracellular iron levels. Furthermore, SS activated the protein kinase RNA-like endoplasmic reticulum kinase/ATF4 endoplasmic reticulum stress pathway by inhibiting glycolysis and promoted ATF3 expression. This process formed a positive feedback loop. In a murine model, SS significantly inhibited glioma cell growth by inducing ferroptosis.Conclusion
These results indicate that SS promotes glioma cell ferroptosis in vitro and in vivo by inhibiting glycolysis through ATF3.
Related
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BibTeX
@article{jia2026atf3,
title = {{ATF3 Promotes Solasonine-Triggered Ferroptosis in Glioma Cells by Suppressing Glycolysis.}},
author = {Mingbo Jia and Hexin Xiao and Minghao Shi and Yao Li and Yang Yang and Jianing Zhao and Zhuoyue Shan and Pengfei Ge and Liyan Zhao},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71226},
url = {https://europepmc.org/article/MED/42921704},
note = {CC BY},
}
RIS
TY - JOUR
TI - ATF3 Promotes Solasonine-Triggered Ferroptosis in Glioma Cells by Suppressing Glycolysis.
AU - Mingbo Jia
AU - Hexin Xiao
AU - Minghao Shi
AU - Yao Li
AU - Yang Yang
AU - Jianing Zhao
AU - Zhuoyue Shan
AU - Pengfei Ge
AU - Liyan Zhao
PY - 2026
DA - 2026/10/01
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71226
UR - https://europepmc.org/article/MED/42921704
AB - Background Glioma cells are characterized by rapid proliferation, a high degree of invasiveness, and significant heterogeneity. Despite the application of various treatment regimens in recent years, the prognosis for glioma remains poor. The induction of ferroptosis in tumor cells has emerged as a promising therapeutic approach. Solasonine (SS), a steroidal alkaloid derived from plants of the Solanaceae family, has multiple antitumor effects. However, whether it can inhibit glioma growth and its mechanism of action have not been studied.Methods The effects of SS on ferroptosis in glioma cells were analyzed by detecting the levels of ferrous ions, reactive oxygen species, and malondialdehyde. The role of activating transcription factor 3 (ATF3) in SS-induced ferroptosis in glioma cells was analyzed using western blotting, immunofluorescence, and confocal microscopy. An in vivo mouse model of glioma was constructed to further investigate the effects of SS.Results We found that SS inhibited the proliferation of glioma cells and promoted their ferroptosis. SS treatment increased the intracellular ferrous ion, malondialdehyde, and reactive oxygen species levels. It increased the intracellular hydrogen peroxide level by regulating ATF3 to inhibit glycolysis and suppress the antioxidant system. Increased hydrogen peroxide levels activated nuclear receptor coactivator 4-dependent ferritinophagy and increased intracellular iron levels. Furthermore, SS activated the protein kinase RNA-like endoplasmic reticulum kinase/ATF4 endoplasmic reticulum stress pathway by inhibiting glycolysis and promoted ATF3 expression. This process formed a positive feedback loop. In a murine model, SS significantly inhibited glioma cell growth by inducing ferroptosis.Conclusion These results indicate that SS promotes glioma cell ferroptosis in vitro and in vivo by inhibiting glycolysis through ATF3.
SN - 1755-5930
SN - 1755-5949
ER -