The activation of artemisinin and its derivatives (ARTs) to generate ROS and other free radicals is mainly heme- or ferrous iron-dependent. ARTs induce ferroptosis in tumor cells, although the involvement of ferroptosis in malaria remains unclear. We found that three typical inducers of ferroptosis (erastin, RSL3 and sorafenib) could effectively mimic DHA inhibition on the growth of blood-stage parasites, which exhibited synergistic or nearly additive interactions in vitro with DHA, while the combination of DHA with ferroptosis inhibitors (deferoxamine, liproxstatin-1) had an obvious antagonistic effect. DHA, similar to ferroptosis inducers, can simultaneously induce the accumulation of ferroptosis-associated cellular labile iron and lipid peroxide. However, deferoxamine and liproxstatin-1 reduced the increase in ferrous iron and lipid peroxide caused by DHA. These results suggested that ferroptosis might be an effective way to induce cell death in parasites and could be a primary mechanism by which DHA kills parasites, with almost 50% contribution at low concentrations. These results provide a new strategy for antimalarial drug screening and clinical medication guidance.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biopha.2022.112742 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synergistic effects of dihydroartemisinin and cisplatin on inducing ferroptosis in gastric cancer through GPX4 inhibition.
Gastric Cancer
December 2024
Department of Gastrointestinal Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China.
Background: In the past several decades, cisplatin (DDP), in combination with other drugs, has been used as the mainstay chemotherapy drug for the treatment of gastric cancer (GC). However, the clinical application of DDP is restricted because of its toxic side effects, it is imperative to explore less toxic and more effective treatment strategies. Dihydroartemisinin (DHA) has been shown to exert potent anticancer effects through ferroptosis in multiple malignancies and has shown high efficacy and safety.
View Article and Find Full Text PDFExogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells.
Transl Oncol
December 2024
Department of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, China. Electronic address:
Ferroptosis is a novel type of programmed cell death caused by excessive iron-dependent lipid peroxidation. According to various studies, there may be a link between ferroptosis and lipid metabolism. However, few studies have been reported on the lipid metabolism of ferroptosis in acute myeloid leukemia (AML).
View Article and Find Full Text PDFBiomineralized apoferritin nanoparticles delivering dihydroartemisinin and calcium for synergistic breast cancer therapy.
Sci Rep
November 2024
Department of International Medicine, The Second Hospital of Dalian Medical University, Dalian, 116000, People's Republic of China.
Breast cancer is one of the most common gynecological malignancies and poses a severe health risk to women. In recent years, ferroptosis therapy has been considered a promising therapeutic strategy for breast cancer by promoting intracellular reactive oxygen species (ROS) production and lipid peroxidation (LPO) accumulation. However, insufficient intracellular ROS levels and suboptimal drug accumulation within breast cancer lesions hinder the efficacy of ferroptosis as a single oncological treatment modality.
View Article and Find Full Text PDFIntestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids.
Nat Commun
November 2024
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Wuhan, 430072, China.
Although the metabolism of yolk lipids such as docosahexaenoic acid (DHA) is pivotal for embryonic development, the underlying mechanism remains elusive. Here we find that the zebrafish hydroxysteroid (17-β) dehydrogenase 12a (hsd17b12a), which encodes an intestinal epithelial-specific enzyme, is essential for the biosynthesis of long-chain polyunsaturated fatty acids in primitive intestine of larval fish. The deficiency of hsd17b12a leads to severe developmental defects in the primitive intestine and exocrine pancreas.
View Article and Find Full Text PDFDesign, synthesis, and in vitro and in vivo biological evaluation of dihydroartemisinin derivatives as potent anti-cancer agents with ferroptosis-inducing and apoptosis-activating properties.
Eur J Med Chem
January 2025
Key Laboratory of Natural Medicines of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address:
Article Synopsis
- * In this study, 41 derivatives of dihydroartemisinin (DHA) were synthesized, with one compound, A3, showing remarkable anti-proliferative effects against cancer cells, 16 times more potent than DHA.
- * Compound A3 works through multiple mechanisms: it regulates key protein expressions that contribute to redox imbalance, triggers ferroptosis, induces apoptosis, and effectively inhibits tumor growth in a mouse model, suggesting it could be a promising anti-cancer drug candidate.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!