Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells
Abstract Breast cancer (BC) remains a leading cause of cancer-related mortality among women, with therapeutic resistance posing significant challenges. This study explores haloperidol (Halo), a clinically approved antipsychotic drug, for its potential antitumoral effects and ability to induce ferrop...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-12645-9 |
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| author | Valeria Consoli Valeria Sorrenti Salvatore Saccone Concetta Federico Francesca Bruno Domenico Andrea Cristaldi Valeria Pittalà Sebastiano Intagliata Luca Vanella |
| author_facet | Valeria Consoli Valeria Sorrenti Salvatore Saccone Concetta Federico Francesca Bruno Domenico Andrea Cristaldi Valeria Pittalà Sebastiano Intagliata Luca Vanella |
| author_sort | Valeria Consoli |
| collection | DOAJ |
| description | Abstract Breast cancer (BC) remains a leading cause of cancer-related mortality among women, with therapeutic resistance posing significant challenges. This study explores haloperidol (Halo), a clinically approved antipsychotic drug, for its potential antitumoral effects and ability to induce ferroptosis, a non-apoptotic programmed cell death linked to oxidative stress and lipid peroxidation. Halo’s activity, partially mediated by sigma (σ) receptors, may enhance chemotherapy efficacy. This investigation delves into the role of heme oxygenase (HO), which was demonstrated to exhibit dual effects in ferroptosis as it’s crucial for the modulation of iron intracellular levels and redox balance. Analysis of main related indicators depict a clear activation of ferroptotic cell death following Halo treatment evidenced by heightened oxidative stress conditions, as indicated by increased lipid peroxidation, elevated reactive oxygen species levels, significant glutathione depletion and mitochondrial membrane potential impairment. Further investigation revealed a protective role of HO-1 and the involvement of ferritinophagic process in MCF-7 BC cells. Additionally, it was evaluated whether Halo effect could be strictly dependent on its activity towards σ receptors and its efficacy in a 3D spheroid model. Data herein reported allow to elucidate Halo triggering of so-called non-canonical ferroptotic pathway suggesting its potential as a candidate for BC treatment. |
| format | Article |
| id | doaj-art-5d4cd49dad6248adb95bf48b04e6df55 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5d4cd49dad6248adb95bf48b04e6df552025-08-20T04:02:45ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-12645-9Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cellsValeria Consoli0Valeria Sorrenti1Salvatore Saccone2Concetta Federico3Francesca Bruno4Domenico Andrea Cristaldi5Valeria Pittalà6Sebastiano Intagliata7Luca Vanella8Department of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment Biological, Geological and Environmental Sciences, University of CataniaDepartment Biological, Geological and Environmental Sciences, University of CataniaDepartment Biological, Geological and Environmental Sciences, University of CataniaCell Dynamics isrlDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaAbstract Breast cancer (BC) remains a leading cause of cancer-related mortality among women, with therapeutic resistance posing significant challenges. This study explores haloperidol (Halo), a clinically approved antipsychotic drug, for its potential antitumoral effects and ability to induce ferroptosis, a non-apoptotic programmed cell death linked to oxidative stress and lipid peroxidation. Halo’s activity, partially mediated by sigma (σ) receptors, may enhance chemotherapy efficacy. This investigation delves into the role of heme oxygenase (HO), which was demonstrated to exhibit dual effects in ferroptosis as it’s crucial for the modulation of iron intracellular levels and redox balance. Analysis of main related indicators depict a clear activation of ferroptotic cell death following Halo treatment evidenced by heightened oxidative stress conditions, as indicated by increased lipid peroxidation, elevated reactive oxygen species levels, significant glutathione depletion and mitochondrial membrane potential impairment. Further investigation revealed a protective role of HO-1 and the involvement of ferritinophagic process in MCF-7 BC cells. Additionally, it was evaluated whether Halo effect could be strictly dependent on its activity towards σ receptors and its efficacy in a 3D spheroid model. Data herein reported allow to elucidate Halo triggering of so-called non-canonical ferroptotic pathway suggesting its potential as a candidate for BC treatment.https://doi.org/10.1038/s41598-025-12645-9HaloperidolCancerFerroptosisOxidative stressHeme oxygenase |
| spellingShingle | Valeria Consoli Valeria Sorrenti Salvatore Saccone Concetta Federico Francesca Bruno Domenico Andrea Cristaldi Valeria Pittalà Sebastiano Intagliata Luca Vanella Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells Scientific Reports Haloperidol Cancer Ferroptosis Oxidative stress Heme oxygenase |
| title | Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells |
| title_full | Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells |
| title_fullStr | Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells |
| title_full_unstemmed | Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells |
| title_short | Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells |
| title_sort | haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells |
| topic | Haloperidol Cancer Ferroptosis Oxidative stress Heme oxygenase |
| url | https://doi.org/10.1038/s41598-025-12645-9 |
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