Frontiers in Pharmacology最新文献

{"title":"Icariin modulates osteogenic and adipogenic differentiation in ADSCs via the Hippo-YAP/TAZ pathway: a novel therapeutic strategy for osteoporosis.","authors":"Shaozi Lin, Zuyu Meng, Mei Wang, Zixuan Ye, Mengsha Long, Yiyao Zhang, Fang Liu, Hongling Chen, Menghan Li, Jiajia Qin, Haiquan Liu","doi":"10.3389/fphar.2024.1510561","DOIUrl":"10.3389/fphar.2024.1510561","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cell (ADSC) transplantation presents a promising approach for osteoporosis (OP) treatment. However, the therapeutic efficacy of ADSCs is hindered by low post-transplantation survival rates and limited capacities for adhesion, migration, and differentiation. Icariin (ICA), the primary active compound of Epimedium, has been shown to promote cell proliferation and induce osteogenic differentiation; however, its specific effects on ADSC osteogenesis and the mechanisms by which ICA enhances osteoporosis treatment through cell transplantation remain inadequately understood.</p><p><strong>Purpose: </strong>This study investigates the effects of different concentrations of ICA on the osteogenic and adipogenic differentiation of rat ADSCs, aiming to elucidate the underlying mechanisms. ADSCs were isolated from female SPF-grade SD rats, with surface markers identified through flow cytometry. Osteogenic and adipogenic differentiation were assessed using Alizarin Red and Oil Red O staining, respectively. Third-generation ADSCs were divided into five groups: control, resveratrol (100 μmol/L), and four ICA treatment groups (1, 10, 50, and 100 μmol/L). Western blotting was performed to analyze the expression of factors associated with the Hippo-YAP/TAZ signaling pathway and the adipogenic marker PPARγ. Additionally, ADSCs were labeled with lentiviruses carrying enhanced green fluorescent protein (EGFP) and 5-bromo-2-deoxyuridine (BrdU) to assess their <i>in vivo</i> distribution, survival, proliferation, and differentiation of ADSCs post-ICA intervention.</p><p><strong>Results: </strong><i>In vitro</i>, ICA significantly inhibited the Hippo pathway, reducing YAP and TAZ phosphorylation and enhancing their transcriptional activity, while simultaneously suppressing PPARγ. This promoted osteogenesis and inhibited adipogenesis in ADSCs. <i>In vivo</i>, ICA-treated ADSCs demonstrated effective distribution, survival, and osteogenic differentiation following subcutaneous injection into allogeneic rats.</p><p><strong>Conclusion: </strong>Our study demonstrates that ICA significantly enhances the osteogenic differentiation of ADSCs while inhibiting adipogenesis, providing novel insights and therapeutic strategies for osteoporosis and related conditions.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1510561"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of acteoside from <i>Cistanche tubulosa</i> on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells.","authors":"Shilei Zhang, Fukai Gong, Jiali Liu, Shuping You, Tao Liu, Jianhua Yang, Junping Hu","doi":"10.3389/fphar.2024.1370264","DOIUrl":"10.3389/fphar.2024.1370264","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the metabolic mechanisms by which acteoside (ACT) isolated from <i>Cistanche tubulosa</i> alleviates cancer-related fatigue (CRF) in a murine model of colon cancer with cachexia.</p><p><strong>Methods: </strong>BALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated behaviors, tumor inhibition rate, and skeletal muscle morphology assessed by hematoxylin-eosin (H&E) staining and electron microscopy were evaluated. Finally, liquid chromatography-mass spectrometry (LC/MS) was employed to investigate alterations in the plasma metabolic profile of tumor-bearing mice with CRF in response to ACT treatment, and the affinity between metabolite-associated proteins and ACT was verified by Surface plasmon resonance (SPR) assay.</p><p><strong>Results: </strong>Our study demonstrated the presence of CRF in the colon cancer mouse model, with the severity of fatigue increasing alongside tumor growth. Administration of ACT ameliorated both tumor burden and PTX-induced muscle fatigue-like behavior. LC/MS analysis identified a panel of differentially regulated metabolites, including trans-aconitine, citric acid, 3-coumaric acid, ephedrine, thymine, cytosine, indole-3-acetic acid, and pantothenol-9. These metabolites were primarily enriched in pathways associated with valine biosynthesis, tyrosine metabolism, tryptophan metabolism, and biosynthesis of pyridine alkaloids. Furthermore, several key enzymes, including CYP3A4, CYP19A1, CYP2E1, TNF, BCL-2, RYR2, and ATP2A1, were identified as potential targets underlying the anti-CRF effects of ACT.</p><p><strong>Conclusion: </strong>This study suggests that ACT derived from <i>C. tubulosa</i> harbors protective properties against cancer-related fatigue mediated by tumor cells.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1370264"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis in kidney disease: a bibliometric analysis from 2012 to 2024.","authors":"Yuxin Hu, Jingyi Tang, Hanzhang Hong, Yexin Chen, Beibei Ye, Ziheng Gao, Gegongming Zhu, Lin Wang, Weijing Liu, Yaoxian Wang","doi":"10.3389/fphar.2024.1507574","DOIUrl":"10.3389/fphar.2024.1507574","url":null,"abstract":"<p><strong>Background and aims: </strong>Ferroptosis, a novel concept of programmed cell death proposed in 2012, in kidney disease, has garnered significant attention based on evidence of abnormal iron deposition and lipid peroxidation damage in the kidney. Our study aim to examine the trends and future research directions in the field of ferroptosis in kidney disease, so as to further explore the target or treatment strategy for clinical treatment of kidney disease.</p><p><strong>Material and methods: </strong>A thorough survey using the Web of Science Core Collection, focusing on literature published between 2012 and 2024 examining the interaction between kidney disease and ferroptosis was conducted. VOSviewer, CiteSpace, and Biblioshiny were used for in-depth scientometric and visualized analyses.</p><p><strong>Results: </strong>From 2012 to 2024, a total of 2,244 articles met the inclusion criteria for final analysis. The number of annual publications in this area of study showed a steady pattern at the beginning of the decade. The top 3 journals with the highest publication output were <i>Renal Failure</i>, <i>Oxidative Medicine And Cellular Longevity</i>, and <i>Biomedicine & Pharmacotherapy</i>. China and the United States had the highest number of publications. Central South University and Guangzhou Medical University as the most active and influential institutions. Documents and citation analysis suggested that Andreas Linkermann, Jolanta Malyszko, and Alberto Ortiz are active researchers, and the research by Scott J. Dixon and Jose Pedro Friedmann Angeli, as the most cited article, are more important drivers in the development of the field. Keywords associated with glutathione, lipid peroxidation, and nitric oxide had high frequency in the early studies. In recent years, however, there has been a shift towards biomarkers, inflammation and necrosis, which indicate current and future research directions in this area.</p><p><strong>Conclusion: </strong>The global landscape of the ferroptosis research in kidney disease from 2012 to 2024 was presented. Basic research and mechanism exploration for renal fibrosis and chronic kidney disease may be a hot spot in the future.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1507574"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Model organisms in respiratory pharmacology 2023.","authors":"Alexandra McCarron, Ranu Surolia, Livia Ruffini","doi":"10.3389/fphar.2024.1540222","DOIUrl":"10.3389/fphar.2024.1540222","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1540222"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol-driven macrophage polarization: unveiling mechanisms and therapeutic potential.","authors":"Panting Wang, Zixi Li, Yixuan Song, Bowei Zhang, Chaofeng Fan","doi":"10.3389/fphar.2024.1516609","DOIUrl":"10.3389/fphar.2024.1516609","url":null,"abstract":"<p><p>Resveratrol, a polyphenolic compound known for its diverse biological activities, has demonstrated multiple pharmacological effects, including anti-inflammatory, anti-aging, anti-diabetic, anti-cancer, and cardiovascular protective properties. Recent studies suggest that these effects are partly mediated through the regulation of macrophage polarization, wherein macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Our review highlights how resveratrol modulates macrophage polarization through various signaling pathways to achieve therapeutic effects. For example, resveratrol can activate the senescence-associated secretory phenotype (SASP) pathway and inhibit the signal transducer and activator of transcription (STAT3) and sphingosine-1-phosphate (S1P)-YAP signaling axes, promoting M1 polarization or suppressing M2 polarization, thereby inhibiting tumor growth. Conversely, it can promote M2 polarization or suppress M1 polarization by inhibiting the NF-κB signaling pathway or activating the PI3K/Akt and AMP-activated protein kinase (AMPK) pathways, thus alleviating inflammatory responses. Notably, the effect of resveratrol on macrophage polarization is concentration-dependent; moderate concentrations tend to promote M1 polarization, while higher concentrations may favor M2 polarization. This concentration dependence offers new perspectives for clinical treatment but also underscores the necessity for precise dosage control when using resveratrol. In summary, resveratrol exhibits significant potential in regulating macrophage polarization and treating related diseases.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1516609"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological action of <i>Angelica sinensis</i> polysaccharides: a review.","authors":"Chunzhen Ren, Yali Luo, Xiaojuan Li, Like Ma, Chunling Wang, Xiaodong Zhi, Xinke Zhao, Yingdong Li","doi":"10.3389/fphar.2024.1510976","DOIUrl":"10.3389/fphar.2024.1510976","url":null,"abstract":"<p><p><i>Angelica sinensis</i>, a traditional Chinese herbal medicine and food, which has a long history of clinical application, is used to improve health conditions and treat various diseases. <i>Angelica sinensis</i> polysaccharides (ASP), the main active component of this traditional Chinese medicine, have multicomponent, multitarget characteristics and very broad pharmacological activities. They play important roles in the treatment of several diseases. In addition, the effect is significant, which may provide a more comprehensive database and theoretical support for applying ASP in the treatment of disease and could be considered a promising candidate for preventing disease. This review summarizes the research progress on the extraction, chemical structure, pharmacological effects, and mechanisms of ASP and its derivatives by reviewing relevant national and international literature and provides comprehensive information and a reliable basis for the exploration of new treatment strategies involving botanical drugs for disease therapy. Literature information was obtained from scientific ethnobotany and ethnomedicine databases (up to September 2024), mainly from the PubMed, Web of Science, and CNKI databases. The literature has explored the extraction, purification, structure, and pharmacological effects of <i>Angelica sinensis</i> polysaccharides. The search keywords for such work included \"<i>Angelica sinensis</i>\" or \"<i>Angelica sinensis</i> polysaccharides,\" and \"<i>pharmacological</i> effects,\" \"extraction\" and \"structure.\" Multiple studies have shown that ASP has important pharmacological effects, such as antitumor, anemia-improving, anti-inflammatory, antioxidative, immunomodulatory, hepatoprotective, antifibrotic, hypoglycemic, antiradiation, and antiviral effects, the mechanisms of which appear to involve the regulation of inflammation, oxidative stress, and profibrotic signaling pathways. As a natural polysaccharide, ASP has potential applications as a drug. However, further research should be undertaken to clarify the unconfirmed regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. This review establishes a theoretical foundation for future studies on the structure, mechanism, and clinical use of ASP.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1510976"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Danshen injection ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibiting ferroptosis via activating SIRT1/GPX4 pathway.","authors":"Yiwen Cao, Huan Zhao, Shuyin Lin, Junqi Chen, Jingli Xiong, Zhijun Zeng, Ziyu Long, Yingru Su, Yingqi Zhong, Lingru Zhao, Mingshan Zhang, Junbiao Wu, Yuan Zhou, Jiuyao Zhou","doi":"10.3389/fphar.2024.1503628","DOIUrl":"10.3389/fphar.2024.1503628","url":null,"abstract":"<p><strong>Introduction: </strong>The pathogenesis of renal fibrosis is related to blood stasis, and the method of promoting blood circulation and removing blood stasis is often used as the treatment principle. Danshen injection (DSI) is a commonly used drug for promoting blood circulation and removing blood stasis in clinic. However, whether DSI slows the progression of renal fibrosis or the potential mechanism is uncertain.</p><p><strong>Methods: </strong>We investigated renal fibrosis models using UUO mice and TGF-β stimulation in HK-2 cells.</p><p><strong>Results: </strong>Our findings revealed that DSI or Fer-1 alleviated kidney injury by ameliorating renal morphology injury and pathological injury <i>in vivo</i>. Besides, DSI or Fer-1 inhibited renal fibrosis <i>in vivo</i> and in TGF-β-induced HK-2 cells. Furthermore, ferroptosis was lessened under DSI or Fer-1 treatment. More importantly, the DSI active ingredients (danshensu, salvianolic acid B, protocatechuic aldehyde, caffeic acid and tanshinone IIA) could bind to SIRT1. The protein levels of SIRT1 and GPX4 were downregulated accompanied by the incremental concentrations of TGF-β or Erastin, which were repaired by DSI or Fer-1 intervention. However, the inhibition of ferroptosis and renal fibrosis owing to DSI were reversed by SIRT1 inhibitor EX527.</p><p><strong>Conclusion: </strong>Taken together, our results indicated that DSI could protect against ferroptosis to attenuate renal fibrosis by activating the SIRT1/GPX4 pathway. It is expected to be a potential agent to treat renal fibrosis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1503628"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clopidogrel combined with rivaroxaban in peripheral artery disease after revascularization.","authors":"Min Lu, Jiaqi Li, Huanyu Ni, Tong Qiao, Baoyan Wang","doi":"10.3389/fphar.2024.1485380","DOIUrl":"10.3389/fphar.2024.1485380","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the efficacy and safety of clopidogrel-rivaroxaban combination compared to aspirin-rivaroxaban combination in patients with symptomatic peripheral artery disease (PAD).</p><p><strong>Methods: </strong>Consecutive patients with symptomatic PAD patients were analyzed from January, 2018 to June, 2022 at Nanjing Drum Tower Hospital. Patients were divided into two groups based on the antithrombotic therapy. The primary efficacy outcome was a composite of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and the primary safety outcome was major bleeding. Patients were followed until the first occurrence of any outcomes or the study end date (30 June 2024).</p><p><strong>Results: </strong>A total of 695 patients were enrolled into this study. The clopidogrel-rivaroxaban combination significantly reduced the risk of composite outcome (HR: 0.59, 95%CI: 0.41-0.83) without increasing the risk of major bleeding (HR: 0.68, 95%CI: 0.27-1.69). When analyzed separately, clopidogrel-rivaroxaban combination was associated with a reduced risk of MALE (HR: 0.61, 95%CI: 0.41-0.91), although no significant differences were observed in terms of MACE (HR: 0.64, 95%CI: 0.34-1.20) or all bleeding events (HR: 1.00, 95%CI: 0.52-1.93). In the subgroup analysis, there were no significant interactions between the treatment groups and the subgroups of age, diabetes, lesion sites, Rutherford classifications and renal function for composite outcome, MACE and MALE.</p><p><strong>Conclusion: </strong>The clopidogrel-rivaroxaban combination in PAD patients may offer enhanced cardiovascular protection without increasing the risk of bleeding complications. These findings suggested that clopidogrel could be a superior alternative to aspirin in dual antithrombotic therapy for PAD management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1485380"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between energy metabolism and NADPH oxidase-mediated pathophysiology in cardiovascular diseases.","authors":"Haipeng Jie, Jingjing Zhang, Shuzhen Wu, Luyao Yu, Shengnan Li, Bo Dong, Feng Yan","doi":"10.3389/fphar.2024.1503824","DOIUrl":"10.3389/fphar.2024.1503824","url":null,"abstract":"<p><p>Sustained production of reactive oxygen species (ROS) and an imbalance in the antioxidant system have been implicated in the development of cardiovascular diseases (CVD), especially when combined with diabetes, hypercholesterolemia, and other metabolic disorders. Among them, NADPH oxidases (NOX), including NOX1-5, are major sources of ROS that mediate redox signaling in both physiological and pathological processes, including fibrosis, hypertrophy, and remodeling. Recent studies have demonstrated that mitochondria produce more proteins and energy in response to adverse stress, corresponding with an increase in superoxide radical anions. Novel NOX4-mediated modulatory mechanisms are considered crucial for maintaining energy metabolism homeostasis during pathological states. In this review, we integrate the latest data to elaborate on the interactions between oxidative stress and energy metabolism in various CVD, aiming to elucidate the higher incidence of CVD in individuals with metabolic disorders. Furthermore, the correlations between NOX and ferroptosis, based on energy metabolism, are preliminarily discussed. Further discoveries of these mechanisms might promote the development of novel therapeutic drugs targeting NOX and their crosstalk with energy metabolism, potentially offering efficient management strategies for CVD.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1503824"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application.","authors":"Murshid Imam, Jiale Ji, Zhijie Zhang, Shunchao Yan","doi":"10.3389/fphar.2024.1493188","DOIUrl":"10.3389/fphar.2024.1493188","url":null,"abstract":"<p><p>Breast cancer is the most commonly diagnosed cancer worldwide. Metal metabolism is pivotal for regulating cell fate and drug sensitivity in breast cancer. Iron and copper are essential metal ions critical for maintaining cellular function. The accumulation of iron and copper ions triggers distinct cell death pathways, known as ferroptosis and cuproptosis, respectively. Ferroptosis is characterized by iron-dependent lipid peroxidation, while cuproptosis involves copper-induced oxidative stress. They are increasingly recognized as promising targets for the development of anticancer drugs. Recently, compelling evidence demonstrated that the interplay between ferroptosis and cuproptosis plays a crucial role in regulating breast cancer progression. This review elucidates the converging pathways of ferroptosis and cuproptosis in breast cancer. Moreover, we examined the value of genes associated with ferroptosis and cuproptosis in the clinical diagnosis and treatment of breast cancer, mainly outlining the potential for a co-targeting approach. Lastly, we delve into the current challenges and limitations of this strategy. In general, this review offers an overview of the interaction between ferroptosis and cuproptosis in breast cancer, offering valuable perspectives for further research and clinical treatment.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1493188"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}