ArticleThe Journal of biological chemistry2014
Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 166 citations in OpenAlex.
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeting ferroptosis to overcome drug resistance in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Overcoming Radiation Resistance: Ferroptosis Induction to Sensitize Solid Tumors to Radiation Therapy.Cancer medicine · 2026Review
- Nutrient stress-induced FTH1 safeguards redox balance and fuels pancreatic ductal adenocarcinoma growth while serving as a therapeutic target and diagnostic biomarker.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- A ferroptosis-based intelligent nanoplatform with chemo-sonodynamic therapy carrying oxygen for improving tumor suppression and antitumor immunity.Journal of nanobiotechnology · 2026Article
- Disruption of iron homeostasis sensitizes pancreatic cancer to irreversible electroporation.Nature communications · 2026Article
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- Overcoming BET-inhibitor JQ1 resistance in aggressive non-small cell lung cancer by inducing ferroptosis via inhibition of the BRD2-FTH1 axis.The FEBS journal · 2025Article
- Current Advances in Anticancer Properties of Heptamethine Carbocyanine DZ-1 Conjugated to Artesunate: Generation of Reactive Oxygen Species.Journal of cellular biochemistry · 2025Article
- Crosstalk between ferroptosis and endoplasmic reticulum stress: A potential target for ovarian cancer therapy (Review).International journal of molecular medicine · 2025Review
- Old drugs, new challenges: reassigning drugs for cancer therapies.Cellular & molecular biology letters · 2025Review
- Hypofractionated radiotherapy (RT) combined with dihydroartemisinin (DHA): No synergistic effect observed in a preliminary animal study.Precision radiation oncology · 2025Article
- Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.Frontiers in oncology · 2025Review
- Downregulation of NCOA4 expression indicates poor prognosis and promotes the progression of cholangiocarcinoma.PloS one · 2025Article
- The Emerging Scenario of Ferroptosis in Pancreatic Cancer Tumorigenesis and Treatment.International journal of molecular sciences · 2024Review
- Natural products targeting ferroptosis pathways in cancer therapy (Review).Oncology reports · 2024Review
- Endoperoxide-enhanced self-assembled ROS producer as intracellular prodrugs for tumor chemotherapy and chemodynamic therapy.Exploration (Beijing, China) · 2024Article
- Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury.Neurochemical research · 2024Review
- Targeted ferritinophagy in gastrointestinal cancer: from molecular mechanisms to implications.Archives of toxicology · 2024Review
- Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.Cell proliferation · 2024Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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Abstract
Artesunate (ART) is an anti-malaria drug that has been shown to exhibit anti-tumor activity, and functional lysosomes are reported to be required for ART-induced cancer cell death, whereas the underlying molecular mechanisms remain largely elusive. In this study, we aimed to elucidate the molecular mechanisms underlying ART-induced cell death. We first confirmed that ART induces apoptotic cell death in cancer cells. Interestingly, we found that ART preferably accumulates in the lysosomes and is able to activate lysosomal function via promotion of lysosomal V-ATPase assembly. Furthermore, we found that lysosomes function upstream of mitochondria in reactive oxygen species production. Importantly, we provided evidence showing that lysosomal iron is required for the lysosomal activation and mitochondrial reactive oxygen species production induced by ART. Finally, we showed that ART-induced cell death is mediated by the release of iron in the lysosomes, which results from the lysosomal degradation of ferritin, an iron storage protein. Meanwhile, overexpression of ferritin heavy chain significantly protected cells from ART-induced cell death. In addition, knockdown of nuclear receptor coactivator 4, the adaptor protein for ferritin degradation, was able to block ART-mediated ferritin degradation and rescue the ART-induced cell death. In summary, our study demonstrates that ART treatment activates lysosomal function and then promotes ferritin degradation, subsequently leading to the increase of lysosomal iron that is utilized by ART for its cytotoxic effect on cancer cells. Thus, our data reveal a new mechanistic action underlying ART-induced cell death in cancer cells.
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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.