ArticleJournal of cancer research and clinical oncology2018
Cell growth potential drives ferroptosis susceptibility in rhabdomyosarcoma and myoblast cell lines.
Article in Journal of cancer research and clinical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 73 citations in OpenAlex.
- Ferroptosis in skeletal muscle: from molecular mechanisms to therapeutic interventions.Journal of orthopaedic translation · 2026Review
- Catalase Defines Radiotherapy Resistance and a Therapeutic Vulnerability in Rhabdomyosarcoma.International journal of molecular sciences · 2026Article
- LCN2-ACOD1 Signalling Affects the Post-Injury Regeneration of Skeletal Muscle Through Mediating Ferroptosis.Cell proliferation · 2026Article
- Ferroptosis-immune crosstalk in CNS diseases: mechanisms and translational insights.Frontiers in immunology · 2026Review
- The synergistic role of ferroptosis in osteosarcoma immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- Dual effects of erastin on aggressive osteosarcoma cells: ferroptosis sensitization and anti-ferroptotic gene activation.Cytotechnology · 2025Article
- Hypoxia induced lipid droplet accumulation promotes resistance to ferroptosis in prostate cancer.Oncotarget · 2025Article
- Caveolin-1 modulates cisplatin sensitivity in oral squamous cell carcinoma through ferroptosis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.Bone research · 2025Review
- Disrupting resistance: novel therapeutic approaches to combat multidrug resistance in fusion-negative rhabdomyosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Advances in ferroptosis in head and neck cancer (Review).Biomedical reports · 2024Review
- Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.Blood advances · 2024Article
- The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.Cancer medicine · 2024Review
- Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects.Experimental hematology & oncology · 2024Review
- A deep insight into ferroptosis in lung disease: facts and perspectives.Frontiers in oncology · 2024Review
- Emerging roles and therapeutic potentials of ferroptosis: from the perspective of 11 human body organ systems.Molecular and cellular biochemistry · 2023Review
- The modulation of iron metabolism affects the Rhabdomyosarcoma tumor growth in vitro and in vivo.Clinical and experimental medicine · 2023Article
- Targeting ferroptosis opens new avenues for the development of novel therapeutics.Signal transduction and targeted therapy · 2023Review
- The dual role of ferroptosis in anthracycline-based chemotherapy includes reducing resistance and increasing toxicity.Cell death discovery · 2023Review
- Patient-derived zebrafish xenografts of uveal melanoma reveal ferroptosis as a drug target.Cell death discovery · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeFerroptosis is a programmed form of iron-dependent cell death caused by lipid hydroperoxide accumulation, which can be prevented by glutathione peroxidase 4 (GPx4) activity. Here we investigated the effects of ferroptosis inducers called erastin and RSL3, which act by glutathione depletion and GPx4 inactivation, respectively, on muscle-derived cell lines of embryonal and alveolar rhabdomyosarcoma (RMS), and mouse normal skeletal C2C12 myoblasts.
methodsMyogenic lines were exposed to stepwise increasing concentrations of ferroptosis inducers either alone or in combination with iron supplementation, iron chelating agents (bathophenanthrolinedisulfonic acid, BPS), antioxidant molecules (glutathione, N-acetylcysteine), lipid peroxidation inhibitors (ferrostatin-1), and chemotherapeutic agents (doxorubicin and actinomycin D). Drug susceptibility was quantified by measuring cell viability, proliferation and differentiation via neutral red assay, crystal violet assay and Giemsa staining, respectively. The detection of lipid hydroperoxide and protein levels was performed by immunofluorescence and Western blot analysis, respectively.
resultsErastin and RSL3 increased lipid hydroperoxide levels preferentially in the embryonal U57810 and myoblast C2C12 lines, leading to ferroptosis that was accentuated by iron supplementation or prevented by co-treatment with BPS, glutathione, N-acetylcysteine and ferrostatin-1. The inhibition of extracellular regulated kinases (ERK) pathway prevented ferroptosis in U57810 and C2C12 cells, whereas its increased activation in the embryonal RD cells mediated by caveolin-1 (Cav-1) overexpression led to augmented ferroptosis susceptibility. Finally, we observed the combination of erastin or RSL3 with chemotherapeutic doxorubicin and actinomycin D agents to be effective in increasing cell death in all RMS lines.
conclusionsErastin and RSL3 trigger ferroptosis in highly proliferating myogenic lines through a ERK pathway-dependent fashion.
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