{"title":"Prescription FINO2 and Pirfenidone Supported in Reducing Fibrosis in Mouse Breast Tumor Tissue by Targeting SLC7A11 and HMOX1.","authors":"Azita Mohammadbeygi, Gholamreza Nikbakht Brujeni, Zohre Eftekhari, Negar Panahi Kazerouni","doi":"10.2174/0115680266353809250526084207","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Breast cancer has become the most commonly diagnosed cancer worldwide and represents a major burden to public health. Advances in understanding ferroptosis pathways and identifying new therapeutic targets raise hope for using ferroptosis modulators to treat untreatable diseases.</p><p><strong>Methods: </strong>In this study, BALB/c mice were divided into several groups: model, Doxorubicintreated, FINO2-treated, Pirfenidone-treated, and a combined Pirfenidone + FINO2 group. After treatment, we assessed iron content in cancer cells, fibrosis area, CD34 expression, and mRNA levels of solute carrier family 7 member 11(SLC7A11) and heme oxygenase 1 (HMOX1).</p><p><strong>Results: </strong>Results showed that the average tumor size in the Pirfenidone + FINO2 group was significantly smaller than in the doxorubicin group. Treatments with FINO2, Pirfenidone, or their combination significantly increased iron content in cancer cells and reduced the fibrosis area. Cotreatment with FINO2 and Pirfenidone also led to notable decreases in CD34 expression and mRNA levels of SLC7A11 and HMOX1.</p><p><strong>Conclusion: </strong>These findings suggest that FINO2 ferroptosis agonists, when combined with other anticancer agents like Pirfenidone, can enhance ferroptosis and reduce tumor fibrosis. Additionally, the overexpression of SLC7A11 and HMOX1 in breast cancer model mice is associated with increased tumor growth and reduced metastasis, indicating that targeting these proteins with specific inhibitors may be a promising strategy for breast cancer treatment.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266353809250526084207","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Breast cancer has become the most commonly diagnosed cancer worldwide and represents a major burden to public health. Advances in understanding ferroptosis pathways and identifying new therapeutic targets raise hope for using ferroptosis modulators to treat untreatable diseases.
Methods: In this study, BALB/c mice were divided into several groups: model, Doxorubicintreated, FINO2-treated, Pirfenidone-treated, and a combined Pirfenidone + FINO2 group. After treatment, we assessed iron content in cancer cells, fibrosis area, CD34 expression, and mRNA levels of solute carrier family 7 member 11(SLC7A11) and heme oxygenase 1 (HMOX1).
Results: Results showed that the average tumor size in the Pirfenidone + FINO2 group was significantly smaller than in the doxorubicin group. Treatments with FINO2, Pirfenidone, or their combination significantly increased iron content in cancer cells and reduced the fibrosis area. Cotreatment with FINO2 and Pirfenidone also led to notable decreases in CD34 expression and mRNA levels of SLC7A11 and HMOX1.
Conclusion: These findings suggest that FINO2 ferroptosis agonists, when combined with other anticancer agents like Pirfenidone, can enhance ferroptosis and reduce tumor fibrosis. Additionally, the overexpression of SLC7A11 and HMOX1 in breast cancer model mice is associated with increased tumor growth and reduced metastasis, indicating that targeting these proteins with specific inhibitors may be a promising strategy for breast cancer treatment.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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