European journal of cell biology最新文献_第2页

Corrigendum to "Viral vaccines promote endoplasmic reticulum stress-induced unfolding protein response in teleost erythrocytes" [Eur. J. Cell Biol. 104 (2025) 151490]. “病毒疫苗促进硬化红细胞内质网应激诱导的展开蛋白反应”的勘误表[欧洲]。[j].中国生物医学工程学报，2016,32(1):387 - 391。

IF 4.3 3区生物学

European journal of cell biology Pub Date : 2025-08-12 DOI: 10.1016/j.ejcb.2025.151510

Maria Salvador-Mira, Paula Gimenez-Moya, Alba Manso-Aznar, Ester Sánchez-Córdoba, Manuel A Sevilla-Diez, Veronica Chico, Ivan Nombela, Sara Puente-Marin, Nerea Roher, Luis Perez, Tanja Dučić, Núria Benseny-Cases, Ana Joaquina Perez-Berna, Maria Del Mar Ortega-Villaizan

引用次数: 0

Interference of estrogen signaling by endocrine disruptors in male and female cells: Potential implications of BPS and PFOS in human development 男性和女性细胞中内分泌干扰物对雌激素信号的干扰：BPS和PFOS在人类发育中的潜在影响

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-20 DOI: 10.1016/j.ejcb.2025.151509

Giulia Gaggi , Andrea Di Credico , Sandra Bibbò , Barbara Corneo , Alberto Ferlin , Angela Di Baldassarre , Barbara Ghinassi

{"title":"Interference of estrogen signaling by endocrine disruptors in male and female cells: Potential implications of BPS and PFOS in human development","authors":"Giulia Gaggi , Andrea Di Credico , Sandra Bibbò , Barbara Corneo , Alberto Ferlin , Angela Di Baldassarre , Barbara Ghinassi","doi":"10.1016/j.ejcb.2025.151509","DOIUrl":"10.1016/j.ejcb.2025.151509","url":null,"abstract":"<div><div>Endocrine-disruptors (EDs), such as bisphenol-S (BPS) and perfluorooctane-sulfonate (PFOS), can cross the placental barrier and interfere with fetal development, inducing consequences that seem to be more pronounced in males. We investigated whether BPS and PFOS could have different effects on male and female human induced-pluripotent-stem cells (hiPSCs) by analyzing their impact on estrogen signaling pathways. Our results demonstrate that in male hiPSCs, BPS and PFOS induce alterations in the estrogen pathways, confirming their role as xenoestrogens. BPS and PFOS also upregulated oxidative phosphorylation proteins in males, while disruptions in Golgi apparatus integrity were observed in female cells. These findings highlight the differential susceptibility of male and female cells to ED exposure and suggest that such chemicals, perturbing the hormonal network, may affect developmental programming and long-term health. Moreover, this study emphasizes the importance of considering sex-specific responses to environmental pollutants and their impact during the highly sensitive periods of fetal growth.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151509"},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Kelch 3 motif on gigaxonin mediates the interaction with NUDCD3 and regulates vimentin filament morphology gigaxonin上的Kelch 3基序介导与NUDCD3的相互作用，并调节vimentin细丝形态

IF 4.3 3区生物学

European journal of cell biology Pub Date : 2025-07-15 DOI: 10.1016/j.ejcb.2025.151508

Cassandra L. Phillips , Christina So , Meredith F. Gillis , Jonathan Harrison , Chih-Hsuan Hsu , Diane Armao , Natasha T. Snider

{"title":"The Kelch 3 motif on gigaxonin mediates the interaction with NUDCD3 and regulates vimentin filament morphology","authors":"Cassandra L. Phillips , Christina So , Meredith F. Gillis , Jonathan Harrison , Chih-Hsuan Hsu , Diane Armao , Natasha T. Snider","doi":"10.1016/j.ejcb.2025.151508","DOIUrl":"10.1016/j.ejcb.2025.151508","url":null,"abstract":"<div><div>Gigaxonin is an intermediate filament (IF)-interacting partner belonging to the Kelch-like (KLHL) protein family. Gigaxonin is encoded by the <em>KLHL16</em> gene, which is mutated in Giant Axonal Neuropathy (GAN). The lack of functional gigaxonin in GAN patient cells impairs IF proteostasis by affecting IF protein degradation and transport. This leads to focal abnormal accumulations of IFs and compromised cellular function, with neurons being most severely impacted. We hypothesized that gigaxonin forms molecular interactions via specific sequence motifs to regulate IF proteostasis. The goal of this study was to examine how distinct Kelch motifs on gigaxonin regulate IF protein degradation and filament morphology. We analyzed vimentin IFs in HEK293 cells overexpressing wild type (WT) gigaxonin, or gigaxonin lacking each of the six individual Kelch motifs, K1-K6. All six gigaxonin deletion mutants (ΔK1-ΔK6) promoted the degradation of soluble vimentin. Compared to WT-gigaxonin, ΔK3-gigaxonin exhibited increased soluble vimentin degradation and increased presence of thick bundles of vimentin IFs. The ΔK4 mutant showed similar, but milder phenotypes compared to ΔK3. Using mass spectrometry proteomics we found that, relative to WT gigaxonin, ΔK3 gigaxonin had increased associations with ubiquitination-associated and mitochondrial proteins but lost the association with the NudC domain-containing protein 3 (NUDCD3), a molecular chaperone enriched in the nervous system. AlphaFold modeling revealed loss of gigaxonin-NUDCD3 binding with ΔK3 and altered binding with ΔK4. Collectively, our cell biological data show the induction of an abnormal GAN-like IF phenotype in cells expressing ΔK3- and, to a lesser extent, ΔK4-gigaxonin, while our proteomic profiling links the loss of gigaxonin-NUDCD3 interactions with defective IF proteostasis.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151508"},"PeriodicalIF":4.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cholangiocarcinoma-derived secreted products and growth arrest-specific 2-like 3 enhance migratory and invasive abilities of fibroblasts 胆管癌衍生的分泌产物和生长抑制特异性2-like 3增强了成纤维细胞的迁移和侵袭能力

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-11 DOI: 10.1016/j.ejcb.2025.151507

Natnicha Paungpan , Kulthida Vaeteewoottacharn , Paweena Dana , Saowaluk Saisomboon , Sittiruk Roytrakul , Wiphawi Hipkaeo , Yada Polsan , Kanlayanee Sawanyawisuth , Sukanya Luang , Worachart Lert-itthiporn , Vor Luvira , Chawalit Pairojkul , Yaovalux Chamgramol , Sopit Wongkham , Seiji Okada

{"title":"Cholangiocarcinoma-derived secreted products and growth arrest-specific 2-like 3 enhance migratory and invasive abilities of fibroblasts","authors":"Natnicha Paungpan , Kulthida Vaeteewoottacharn , Paweena Dana , Saowaluk Saisomboon , Sittiruk Roytrakul , Wiphawi Hipkaeo , Yada Polsan , Kanlayanee Sawanyawisuth , Sukanya Luang , Worachart Lert-itthiporn , Vor Luvira , Chawalit Pairojkul , Yaovalux Chamgramol , Sopit Wongkham , Seiji Okada","doi":"10.1016/j.ejcb.2025.151507","DOIUrl":"10.1016/j.ejcb.2025.151507","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a highly aggressive cancer with limited treatment options, which highlights the urgent need for alternative therapies. One hallmark of CCA is an increase in cancer-associated fibroblasts (CAFs) accompanied by a desmoplastic reaction and fibrosis. However, the roles of CCA-secreted products in fibroblast recruitment remain unclear. This study aimed to identify the chemotactic factors in CCA-secreted products including conditioned media (CCA-CM) and exosomes that promote fibroblast recruitment. The effects of the CCA-CM and exosomes on fibroblast migration and invasion were assessed. The exosomal protein content was analyzed by tandem mass spectrometry. The role of the selected candidate protein, growth arrest-specific 2-like 3 (GAS2L3), in promoting fibroblast migration was investigated using immortalized fibroblasts and CCA-derived CAFs. These results demonstrated that both CCA-CM and exosomes significantly enhanced fibroblast migration, with GAS2L3 playing a critical role in this process. The involvement of CCA-CM and GAS2L3 in fibroblast recruitment was confirmed in clinical CAFs. To our knowledge, this study provides the first evidence that CCA-derived secreted products and GAS2L3 enhance fibroblast migration. These findings suggest CCA-derived GAS2L3 represents a novel therapeutic target for disrupting the interactions between CCA and CAFs, potentially hindering fibroblast recruitment during CCA treatment.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151507"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A diverse interactome of the molecular chaperone CCT/TRiC monomers 分子伴侣CCT/TRiC单体的多种相互作用

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-09 DOI: 10.1016/j.ejcb.2025.151506

Carmen M. Córdoba-Beldad, Julie Grantham

引用次数: 0

Vimentin intermediate filaments facilitate transportation of hepatitis C virus components 弧菌素中间丝促进丙型肝炎病毒成分的运输

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-05 DOI: 10.1016/j.ejcb.2025.151505

Yifan Xing , Shuzhi Cui , Xinyi Huang , Weisong Zhao , Haoyu Li , Jing Zhao , Wakam Chang , Shuangshuang Zhao , Jin Zhong , Yuxin Chen , Yaming Jiu

{"title":"Vimentin intermediate filaments facilitate transportation of hepatitis C virus components","authors":"Yifan Xing , Shuzhi Cui , Xinyi Huang , Weisong Zhao , Haoyu Li , Jing Zhao , Wakam Chang , Shuangshuang Zhao , Jin Zhong , Yuxin Chen , Yaming Jiu","doi":"10.1016/j.ejcb.2025.151505","DOIUrl":"10.1016/j.ejcb.2025.151505","url":null,"abstract":"<div><div>Vimentin, an intermediate filament protein, primarily contributes to intracellular organization, cell migration, and signal transduction. In recent years, the role of intermediate filaments in viral infection has garnered increasing attention. During viral infection, vimentin can regulate viral propagation by forming a vimentin cage to enclose viral replication factories, and facilitating the intracellular transport of viral components. However, whether vimentin can facilitate cell-to-cell transfer of viral components remains unknown. In this study, using hepatitis C virus (HCV) as a viral model, we demonstrated that HCV infection does not induce large-scale vimentin rearrangement or the formation of a vimentin cage. Interestingly, we observed that HCV components move directionally along a vimentin-containing cellular bridge from highly infected donor cells towards neighboring cells, potentially facilitating viral dissemination. Together, our findings unveil a previously unrecognized function of vimentin in the viral life cycle, expanding our understanding of the complex interplay between host cellular factors and viral strategies.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151505"},"PeriodicalIF":4.5,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myosin inhibition enhances cardiomyocyte cell cycle activity through SIRT1-NFAT-mediated H3K9me3 modification 肌球蛋白抑制通过sirt1 - nfat介导的H3K9me3修饰增强心肌细胞周期活性

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-04 DOI: 10.1016/j.ejcb.2025.151504

Rui Jiang , Jiayu Chen , Lijuan Pei , Shiqi Huang , Mengying Feng , Zhaohui Ouyang , Min Yuan , Yalin Zhu , Su Yao , Fenglian He , Hongjie Zhang , Xin Dong , Peng Xie , Ke Wei

{"title":"Myosin inhibition enhances cardiomyocyte cell cycle activity through SIRT1-NFAT-mediated H3K9me3 modification","authors":"Rui Jiang , Jiayu Chen , Lijuan Pei , Shiqi Huang , Mengying Feng , Zhaohui Ouyang , Min Yuan , Yalin Zhu , Su Yao , Fenglian He , Hongjie Zhang , Xin Dong , Peng Xie , Ke Wei","doi":"10.1016/j.ejcb.2025.151504","DOIUrl":"10.1016/j.ejcb.2025.151504","url":null,"abstract":"<div><div>The limited regenerative capacity in adult mammalian heart is mainly attributed to the low cell cycle activity of cardiomyocytes. Achieving cardiomyocyte division is a challenging undertaking, as the contractile function, a major characteristic of cardiomyocytes, is not overall compatible with cell cycle progression. To dissect the relationship between sarcomeric contraction and proliferation in cardiomyocytes, we utilized Blebbistatin (Blebb), a Myosin II inhibitor commonly used for cardiomyocyte culture <em>ex vivo</em>, and revealed that Myosin inhibition by Blebb in cardiomyocytes resulted in enhanced cell cycle entry with cytokinesis failure, thus increasing polyploidy. Elevated H3K9me3 modification was found to be required for the increased cell cycle entry induced by Blebb, and the increased H3K9me3 modifications were enriched on genes that encode negative regulators of cell cycle and controlled by NFAT transcription factors. Furthermore, SIRT1 was identified to be a nucleocytoplasmic shuttling protein that dissociates from Z lines of sarcomeres and translocates into the nucleus upon Myosin inhibition, directly interacts with NFATc3, and is required for the Blebb-induced elevation of H3K9me3 modification and cell cycle activity. Our results identified a signaling pathway transducing sarcomeric signals to epigenetic modifications modulating the cardiomyocyte cell cycle, which may facilitate the understanding of the complex regulatory network controlling cardiomyocyte proliferation and provide therapeutic targets for regenerative medicine.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151504"},"PeriodicalIF":4.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cadmium exposure triggers vimentin phosphorylation via SIRT6-regulated AKT/PI3K signaling pathway in COPD 镉暴露在COPD中通过sirt6调节的AKT/PI3K信号通路触发波形蛋白磷酸化

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-01 DOI: 10.1016/j.ejcb.2025.151503

Rajesh Sinha , Pooja Singh , Huaxiu Zeng, Abhishek Kumar, Veena B. Antony

{"title":"Cadmium exposure triggers vimentin phosphorylation via SIRT6-regulated AKT/PI3K signaling pathway in COPD","authors":"Rajesh Sinha , Pooja Singh , Huaxiu Zeng, Abhishek Kumar, Veena B. Antony","doi":"10.1016/j.ejcb.2025.151503","DOIUrl":"10.1016/j.ejcb.2025.151503","url":null,"abstract":"<div><div>Chronic Obstructive pulmonary disease (COPD) is a global health concern affecting over 300 million individuals worldwide, with airway fibrosis and subsequent small airway narrowing identified as the primary mechanism driving disease progression. This pathological process is characterized by accelerating lung aging, manifesting as reduced cellular growth and increased expression of cyclin-dependent kinase inhibitors in fibroblasts, which we have demonstrated in our previous study utilizing a cadmium-induced COPD mouse model. Cadmium, a toxic heavy metal, penetrates deep into the lung airways inducing oxidative stress, promoting extracellular matrix deposition, and triggering inflammatory reactions. The present study elucidates that cadmium exposure results in the inhibition of sirtuin-6 (SIRT6) which promotes phosphorylation of the AKT/PI3K signaling pathway, which in turn leads to phosphorylation of vimentin, an intermediate filament protein. Cadmium increases extracellular vimentin which is phosphorylated through AKT/PI3K signaling due to SIRT6 inhibition. Vimentin inhibition using siRNA transfection study suggested no effect on SIRT6, phosphorylated AKT and PI3K expression. SIRT6 induction (UBCS039) in fibroblasts leads to a decrease in phosphorylated AKT/PI3K inhibiting extracellular vimentin levels (P = 0.0002) in cadmium-exposed cells. The present work proposes role of SIRT6 in regulation of vimentin, an important intermediate filament in pathogenesis of COPD.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151503"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated phenotypic and transcriptomic characterization of desmin-related cardiomyopathy in hiPSC-derived cardiomyocytes and machine learning-based classification of disease features hipsc衍生心肌细胞中desmin相关心肌病的综合表型和转录组学特征和基于机器学习的疾病特征分类

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-07-01 DOI: 10.1016/j.ejcb.2025.151502

Vivien Batoumeni , Yeranuhi Hovhannisyan , Bénédicte Gobert , Keyhan Alvandipour , Jennifer Arthur Ataam , Ombline Conrad , David Hoffmann , Nicolas Wiest-Daesslé , Jochen Dobner , José Américo Nabuco Leva Ferreira Freitas , Hakim Hocini , Zhenlin Li , Laurent Brino , Andrea Rossi , Onnik Agbulut , Peter Sommer , Pierre Joanne , Konstantinos Gkatzis

{"title":"Integrated phenotypic and transcriptomic characterization of desmin-related cardiomyopathy in hiPSC-derived cardiomyocytes and machine learning-based classification of disease features","authors":"Vivien Batoumeni , Yeranuhi Hovhannisyan , Bénédicte Gobert , Keyhan Alvandipour , Jennifer Arthur Ataam , Ombline Conrad , David Hoffmann , Nicolas Wiest-Daesslé , Jochen Dobner , José Américo Nabuco Leva Ferreira Freitas , Hakim Hocini , Zhenlin Li , Laurent Brino , Andrea Rossi , Onnik Agbulut , Peter Sommer , Pierre Joanne , Konstantinos Gkatzis","doi":"10.1016/j.ejcb.2025.151502","DOIUrl":"10.1016/j.ejcb.2025.151502","url":null,"abstract":"<div><div>Desmin-related diseases are characterized by skeletal muscle weakness, cardiomyopathy, and respiratory dysfunction due to mutations in the desmin gene (<em>DES</em>), which encodes a protein essential for muscle cell integrity. This study investigates the effects of a pathogenic desmin mutation (<em>DES</em><sup>E439K</sup>) in human cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) obtained from a patient carrying the <em>DES</em><sup>E439K</sup> mutation, compared to cardiomyocytes derived from hiPSCs of three healthy donors. To further validate our findings a genome edited cell line has been obtained following the insertion of the mutation in a control hiPSC line. Using advanced technologies, including transcriptomics and phenotypic machine learning algorithms, we analyzed how this mutation disrupts cellular function and contributes to disease phenotypes. Our findings reveal that cardiomyocytes carrying <em>DES</em><sup>E439K</sup> exhibit cytoplasmic protein aggregation, mitochondrial and sarcomere defects, and contractile dysfunctions, highlighting key phenotypic defects in desmin-related cardiomyopathy. Finaly, we developed a machine learning prediction model to classify cellular phenotypes, which can be used for translational research, including drug candidate screening. This research opens new avenues for understanding the molecular mechanisms of desmin-related cardiomyopathies and fosters the development of novel therapeutic strategies.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151502"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ropivacaine and lidocaine inhibit SaOS-2 osteosarcoma cell proliferation and invasion via mitochondrial dysfunction and apoptosis 罗哌卡因和利多卡因通过线粒体功能障碍和凋亡抑制SaOS-2骨肉瘤细胞的增殖和侵袭

IF 4.5 3区生物学

European journal of cell biology Pub Date : 2025-06-24 DOI: 10.1016/j.ejcb.2025.151501

Inna Zumberg, Amir Hashemi, Masoumeh Ezati, Larisa Chmelikova, Katerina Ingrova, Vratislav Cmiel

{"title":"Ropivacaine and lidocaine inhibit SaOS-2 osteosarcoma cell proliferation and invasion via mitochondrial dysfunction and apoptosis","authors":"Inna Zumberg, Amir Hashemi, Masoumeh Ezati, Larisa Chmelikova, Katerina Ingrova, Vratislav Cmiel","doi":"10.1016/j.ejcb.2025.151501","DOIUrl":"10.1016/j.ejcb.2025.151501","url":null,"abstract":"<div><div>Local anesthetics are routinely used for pain management, yet their broader effects on cancer cells remain incompletely understood. Here, we investigate the impact of ropivacaine hydrochloride and lidocaine hydrochloride monohydrate on SaOS-2 human osteosarcoma cells using a series of <em>in vitro</em> assays. Our findings indicate that both anesthetics markedly reduce cell viability and proliferation, as measured by XTT and Colony formation assays, respectively. Mechanistic studies reveal significant disruption of mitochondrial function, evidenced by decreased membrane potential, enhanced mitochondrial superoxide production, and pronounced mitochondrial fragmentation. Concurrently, the expression of matrix metalloproteinases (MMP-2 and MMP-9) is downregulated, while pro-apoptotic markers (Caspase-3, Caspase-9, and BAX) are upregulated. Neither agent alters Vimentin or E-cadherin expression, suggesting a limited effect on epithelial-mesenchymal transition pathways. Notably, lidocaine and ropivacaine also inhibit SaOS-2 cell migration and invasion, as demonstrated by Scratch, single-cell migration, and Transwell invasion assays. Furthermore, both agents suppress alkaline phosphatase activity, a hallmark associated with osteosarcoma differentiation and metastatic potential. Taken together, these results support the conclusion that ropivacaine and lidocaine exert broad anti-tumor effects by impairing both mitochondrial homeostasis and the invasive phenotype in osteosarcoma cells. Their capacity to mitigate core hallmarks of malignancy underscores the need for further investigation into local anesthetics as potential adjuvant therapies for osteosarcoma.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 3","pages":"Article 151501"},"PeriodicalIF":4.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0