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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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
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Ferroptosis: process and function
Xie, Y., Hou, W., Song, X., Yu, Y., Huang, J., Sun, X., Kang, R., & Tang, D. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.158 · Cited by 3,727
Ferroptosis: Death by Lipid Peroxidation
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Broadening horizons: the role of ferroptosis in cancer
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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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