Title:Artesunate Inhibits the Growth of Insulinoma Cells via SLC7A11/
GPX4-mediated Ferroptosis
Volume: 30
Issue: 3
Author(s): Fengping Chen, Jiexia Lu, Biaolin Zheng, Nan Yi, Chunxiao Xie, Feiran Chen, Dafu Wei, Haixing Jiang*Shanyu Qin*
Affiliation:
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Keywords:
Artesunate, ferroptosis, insulinoma, neuroendocrine tumors, SLC7A11, GPX4.
Abstract:
Background: Artesunate (ART) has been recognized to induce ferroptosis in various tumor phenotypes,
including neuroendocrine tumors. We aimed to investigate the effects of ART on insulinoma and the underlying
mechanisms by focusing on the process of ferroptosis.
Methods: The CCK8 and colony formation assays were conducted to assess the effectiveness of ART. Lipid
peroxidation, glutathione, and intracellular iron content were determined to validate the process of ferroptosis,
while ferrostatin-1 (Fer-1) was employed as the inhibitor of ferroptosis. Subcutaneous tumor models were
established and treated with ART. The ferroptosis-associated proteins were determined by western blot and immunohistochemistry
assays. Pathological structures of the liver were examined by hematoxylin-eosin staining.
Results: ART suppressed the growth of insulinoma both in vitro and in vivo. Insulinoma cells treated by ART
revealed signs of ferroptosis, including increased lipid peroxidation, diminished glutathione levels, and ascending
intracellular iron. Notably, ART-treated insulinoma cells exhibited a decline in the expressions of catalytic
component solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). These alterations
were negated by Fer-1. Moreover, no hepatotoxicity was observed upon the therapeutic dose of ART.
Conclusion: Artesunate might regulate ferroptosis of insulinoma cells through the SLC7A11/GPX4 pathway.
