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- Title
Dihydroartemisinin induces ferroptosis in T cell acute lymphoblastic leukemia cells by downregulating SLC7A11 and activating the ATF4‑CHOP signaling pathway.
- Authors
Tang, Na; Liu, Xinling; Liu, Yong; Wang, Haihua; Zhao, Yao; Wang, Haiying; Hu, Zhenbo
- Abstract
The present study aimed to investigate the anti-leukemic effects of dihydroartemisinin (DHA) on T-cell acute lymphoblastic leukemia (T-ALL) cell lines, Jurkat and Molt-4, and the underlying mechanisms. Cell Counting Kit-8 was performed to measure cell viability. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The expression levels of ATF4 and CHOP mRNA were assessed by reverse transcription-quantitative PCR, while the protein abundance of SLC7A11, GPX4, ATF4 and CHOP was determined by western blotting. Moreover, malondialdehyde, glutathione (GSH) and reactive oxygen species (ROS) assays were used to detect the levels of ferroptosis. The results showed that DHA suppressed T-ALL cell viability in vitro, and induced cell cycle arrest at S or G2/M phase. DHA also induced ROS burst, activated endoplasmic reticulum (ER) stress, disrupted the system Xc−-GSH-GSH peroxidase 4 antioxidant system, and increased lipid peroxide accumulation, resulting in cell death. By contrast, the pharmacological inhibition of ferroptosis alleviated DHA-induced cell death, confirming that DHA induces T-ALL cell death via ferroptosis. Mechanistically, the effect of DHA on ferroptosis was partly mediated by downregulating SLC7A11 and upregulating the ATF4-CHOP signaling pathway, which is associated with ER stress. These results indicated that DHA may induce ferroptosis in T-ALL cell lines and could represent a promising therapeutic agent for treating T-ALL.
- Subjects
LYMPHOBLASTIC leukemia; ACUTE leukemia; GLUTAMATE transporters; CELL cycle; T cells
- Publication
Oncology Letters, 2024, Vol 28, Issue 1, pN.PAG
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2024.14470