The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells
Open accessAbstract
Oncogenic KRas reprograms pancreatic ductal adenocarcinoma (PDAC) cells to states which are highly resistant to apoptosis. Thus, a major preclinical goal is to identify effective strategies for killing PDAC cells. Artesunate (ART) is an anti-malarial that specifically induces programmed cell death in different cancer cell types, in a manner initiated by reactive oxygen species (ROS)-generation. In this study we demonstrate that ART specifically induced ROS- and lysosomal iron-dependent cell death in PDAC cell lines. Highest cytotoxicity was obtained in PDAC cell lines with constitutively-active KRas, and ART did not affect non-neoplastic human pancreatic ductal epithelial (HPDE) cells. We determined that ART did not induce apoptosis or necroptosis. Instead, ART induced ferroptosis, a recently described mode of ROS- and iron-dependent programmed necrosis which can be activated in Ras-transformed cells. Co-treatment with the ferroptosis inhibitor ferrostatin-1 blocked ART-induced lipid peroxidation and cell death, and increased long-term cell survival and proliferation. Importantly, analysis of PDAC patient mRNA expression indicates a dependency on antioxidant homeostasis and increased sensitivity to free intracellular iron, both of which correlate with Ras-driven sensitivity to ferroptosis. Overall, our findings suggest that ART activation of ferroptosis is an effective, novel pathway for killing PDAC cells.
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“Of note, artemisinin derivatives have been reported to induce iron-dependent cell death, and specifically ferroptosis”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [85]
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Metadata
- Authors
- Eling, N., Reuter, L., Hazin, J., Hamacher-Brady, A., & Brady, N. R.
- Affiliations
- German Cancer Research Center (DE)
- Lysosomal Systems Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Venue
- Oncoscience
- Publisher
- Impact Journals, LLC
- Published
- 2015-05-02
- Volume
- 2
- Issue
- 5
- Pages
- 517-532
- ISSN
- 2331-4737 (ISSN-L)
- PMC
- PMC4468338
- OpenAlex
- W2418439210
- Cited by
- 524
- References
- 59
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 57 · 2023: 71 · 2022: 92 · 2021: 91 · 2020: 60 · 2019: 26 · 2018: 21 · 2017: 23 · 2016: 15 · 2015: 2
- FWCI
- 16.10
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncoscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- Bundesministerium für Bildung und Forschung
- University of Toronto
- Tianjin Medical University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- artesunate, ferroptosis, pancreatic ductal adenocarcinoma, reactive oxygen species, lysosomal iron, lipid peroxidation, ferrostatin-1, antioxidant homeostasis, necroptosis, apoptosis resistance, anticancer drug repurposing
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