ArticleProceedings of the National Academy of Sciences of the United States of America2019
Exquisite sensitivity of adrenocortical carcinomas to induction of ferroptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Microenvironment immune response induced by tumor ferroptosis-the application of nanomedicine.Frontiers in oncology · 2022Pooled it
- FerroScore: a statistical approach for quantifying tumor-related ferroptosis based on omics data.Briefings in bioinformatics · 2026Article
- Integrated metabolome and transcriptome analysis reveals ferroptosis involvement in cisplatin resistance of esophageal squamous cancer cell.Computational and structural biotechnology journal · 2026Article
- Article
- Selenium and selenoproteins: key regulators of ferroptosis and therapeutic targets in cancer.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Growth hormone-releasing hormone and cancer.Reviews in endocrine & metabolic disorders · 2025Review
- A targetable antioxidant defense mechanism to EZH2 inhibitors enhances tumor cell vulnerability to ferroptosis.Cell death & disease · 2025Article
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
- Ferroptosis in health and disease.Redox biology · 2024Review
- Ferroptosis-based advanced therapies as treatment approaches for metabolic and cardiovascular diseases.Cell death and differentiation · 2024Review
- Ferroptosis-Related lncRNA to Predict the Clinical Outcomes and Molecular Characteristics of Kidney Renal Papillary Cell Carcinoma.Current issues in molecular biology · 2024Article
- Emerging roles and therapeutic potentials of ferroptosis: from the perspective of 11 human body organ systems.Molecular and cellular biochemistry · 2023Review
- Identification of the ferroptosis regulator HELLS with prognostic value for adrenocortical carcinoma based on integrated analysis and experimental validation.Gland surgery · 2023Article
- Selenium in Prostate Cancer: Prevention, Progression, and Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- vPIF-1 is an insulin-like antiferroptotic viral peptide.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Effects of o,p'-DDE, a Mitotane Metabolite, in an Adrenocortical Carcinoma Cell Line.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Ferroptosis in tumor immunity and therapy.Journal of cellular and molecular medicine · 2022Review
- Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers.Biomolecules · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adrenocortical carcinomas (ACCs) are rare and highly malignant cancers associated with poor survival of patients. Currently, mitotane, a nonspecific derivative of the pesticide DDT (1,1-(dichlorobiphenyl)-2,2-dichloroethane), is used as the standard treatment, but its mechanism of action in ACCs remains elusive. Here we demonstrate that the human ACC NCI-H295R cell line is remarkably sensitive to induction of ferroptosis, while mitotane does not induce this iron-dependent mode of regulated necrosis. Supplementation with insulin, transferrin, and selenium (ITS) is commonly used to keep NCI-H295R cells in cell culture. We show that this supplementation prevents spontaneous ferroptosis, especially when it contains polyunsaturated fatty acids (PUFAs), such as linoleic acid. Inhibitors of apoptosis (zVAD, emricasan) do not prevent the mitotane-induced cell death but morphologically prevent membrane blebbing. The expression of glutathione peroxidase 4 (GPX4) in H295R cells, however, is significantly higher when compared to HT1080 fibrosarcoma cells, suggesting a role for ferroptosis. Direct inhibition of GPX4 in H295R cells led to high necrotic populations compared to control, while cotreatment with ferrostatin-1 (Fer-1) completely reverted ferroptosis. Interestingly, the analysis of public databases revealed that several key players of the ferroptosis pathway are hypermethylated and/or mutated in human ACCs. Finally, we also detected that growth hormone-releasing hormone (GHRH) antagonists, such as MIA602, kill H295R cells in a nonapoptotic manner. In summary, we found elevated expression of GPX4 and higher sensitivity to ferroptosis in ACCs. We hypothesize that instead of treatment with mitotane, human adrenocortical carcinomas may be much more sensitive to induction of ferroptosis.
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