ArticleScientific reports2025
Potent ferroptosis agent RSL3 induces cleavage of Pyroptosis-Specific gasdermins in Cancer cells.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Ferroptosis-inflammasome crosstalk contributes to hyperglycemia-induced neuronal injury and is modulated by the ferroptosis inhibitor UAMC-3203.Molecular biology reports · 2026Article
- Cutibacterium acnes-Derived Extracellular Vesicles Promote Epithelial Ovarian Cancer Progression by Activating the KEAP1-NRF2 Antioxidant Pathway to Suppress Ferroptosis.Microbial biotechnology · 2026Article
- Phase I trial of the combination of bortezomib and clofarabine in adults with refractory tumors.Cancer chemotherapy and pharmacology · 2026Article
- Advances in ferroptosis mechanisms and therapeutic potential in head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2026Review
- Inflammasome-associated pyroptosis and tumor angiogenesis in prostate cancer.Iranian journal of basic medical sciences · 2026Review
- Fundamental mechanism of ferroptosis: Three unanswered questions.Ferroptosis and oxidative stress · 2026Article
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Emerging small molecule strategies target cancer stem cells through ferroptosis and metabostemness.Discover oncology · 2025Review
- A lactylation-ferroptosis cross-talk gene signature predicts hepatocellular carcinoma prognosis and reveals STMN1/PRDX1 as therapeutic targets.Frontiers in immunology · 2025Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a form of iron-dependent cell death of interest for the development of novel anti-cancer therapies. Ferroptosis research uses a process of elimination based on assumed ferroptosis-specific inducers and inhibitors; these molecules however have off-target effects and cannot provide a comprehensive picture of overlapping pathways. We investigated whether pyroptosis-a form of inflammatory cell death-is initiated in cancer cells following treatment with the ferroptosis inducer RSL3. We treated 6 cancer cell lines with RSL3 alone or in combination with inhibitors of ferroptosis (Ferrostatin-1), caspases (zVADfmk), necroptosis (Necrostatin-1), BID (BI-6C9), or STING (H-151). Biomarkers of pyroptosis and ferroptosis were assessed using our novel quantitative multiplex immunoassay. Increased secretion of pyroptosis-associated cytokines (IL-1α, IL-1β, IL-18), and gasdermin D and E (GSDMD/E) cleavage with parallel loss of respective full-length proteins-both hallmarks of pyroptosis-were recorded in 5/6 cell lines following RSL3 treatment. RSL3 cytotoxicity was blocked by Ferostatin-1; BID and STING inhibitors also prevented GSDMD/E cleavage. We conclude that the ferroptosis-inducer RSL3 triggers pyroptosis in cancer cells; further work is required to elucidate the role of mitochondria in this process. Measurement of pathway-specific protein biomarkers is therefore necessary to identify the exact mechanism of action of novel cytotoxic agents.
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