ArticleAmerican journal of cancer research2021
Artesunate induces ER-derived-ROS-mediated cell death by disrupting labile iron pool and iron redistribution in hepatocellular carcinoma cells.
Article in American journal of cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Tumoricidal efficacy of DZ-1 dye conjugated to dihydroartemisinin in patient-derived colorectal liver metastasis tumoroids.Molecular therapy. Oncology · 2026Article
- Artesunate directly targets glucosylceramidase to suppress hepatocellular carcinoma proliferation and trigger apoptosis.Genes & diseases · 2026Article
- MnUA-DOX-artesunate hydrogel remodels immunosuppressive tumor microenvironment and prevents postoperative recurrence in triple-negative breast cancer.Journal of nanobiotechnology · 2026Article
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Current Advances in Anticancer Properties of Heptamethine Carbocyanine DZ-1 Conjugated to Artesunate: Generation of Reactive Oxygen Species.Journal of cellular biochemistry · 2025Article
- Multiple entanglements of different cell death pathways, in which caspase-8 and BID interact with cardiolipin*, have been identified.Frontiers in cell and developmental biology · 2025Review
- Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediatedOpen life sciences · 2025Article
- Ferroptosis and its Potential Determinant Role in Myocardial Susceptibility to Ischemia/Reperfusion Injury in Diabetes.Reviews in cardiovascular medicine · 2024Review
- Artemisinin and Its Derivatives as Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2024Review
- Tween 80 Micelles Loaded with FePharmaceutics · 2024Article
- Ferroptotic therapy in cancer: benefits, side effects, and risks.Molecular cancer · 2024Review
- Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma.Heliyon · 2024Review
- Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations.International journal of nanomedicine · 2024Review
- Enhancement of Anticancer Potential of Artemisinin Derivatives through N-glycosylation.Current topics in medicinal chemistry · 2024Review
- Anti-tumor mechanism of artesunate.Frontiers in pharmacology · 2024Review
- The Antimalarial Drug Artesunate Mediates Selective Cytotoxicity by Upregulating HO-1 in Melanoma Cells.Biomedicines · 2023Article
- Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties.Antioxidants (Basel, Switzerland) · 2023Review
- The Emerging Role of Ferroptosis in Liver Cancers.Life (Basel, Switzerland) · 2022Review
- Preclinical investigation of artesunate as a therapeutic agent for hepatocellular carcinoma via impairment of glucosylceramidase-mediated autophagic degradation.Experimental & molecular medicine · 2022Article
- The Labile Iron Pool Reacts Rapidly and Catalytically with Peroxynitrite.Biomolecules · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant iron homeostasis is a typical characteristic of Hepatocellular carcinoma (HCC), and perturbation of iron metabolism is an effective strategy for HCC therapy. However, there are few safe and effective targeting agents available in clinical practices. The artemisinin and its derivatives have shown potential anti-cancer activity by disturbing cellular iron homeostasis, but the specific mechanism is still unclear. In this study, we demonstrate that Artesunate (ART), a water-soluble anti-malaria agent in clinical use, can regulate the labile iron pool (LIP) and effectively induce ROS-dependent cell death in multiple HCC cells. Mechanistically, ART increases the LIP by promoting lysosomal degradation of iron-storage protein ferritin through acidizing lysosomes. Then the accumulation of labile iron in the endoplasmic reticulum (ER) promotes excessive reactive oxygen species (ROS) production and severe ER disruption, which leads to cell death. Our results provide a new understanding of how ART modulates iron metabolism in HCC cells at the subcellular level, demonstrate the significance of endoplasmic reticulum as iron-vulnerability of HCC cells. More importantly, our findings suggest ART is a safe and potential anti-HCC agent via disturbing iron homeostasis.
Indexed as
Identifiers
33791148PMC7994160W3147657981What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.