{"title":"Imipramine-induced Apoptosis and Metastasis Inhibition in Human Bladder Cancer T24 Cells Through EGFR/ERK/NF-κB Pathway Suppression.","authors":"Wei-Shu Wang, Yu-Chang Liu, Tsai-Lin Lo, Fei-Ting Hsu, Chih-Hung Chiang","doi":"10.21873/invivo.13871","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Bladder cancer is a prevalent malignancy, ranging from superficial forms to more aggressive types that invade the muscle and require extensive treatment. Imipramine, traditionally used as an antidepressant, has shown potential as an anti-cancer agent.</p><p><strong>Materials and methods: </strong>In this study, human bladder cancer T24 cells were treated with varying concentrations of imipramine to evaluate its cytotoxic and apoptotic effects.</p><p><strong>Results: </strong>Imipramine induced cytotoxicity in a dose-dependent manner, significantly increasing apoptosis as shown by Annexin-V/PI staining and TUNEL assay. The drug also up-regulated cleaved caspase-3 and down-regulated the anti-apoptotic factor XIAP. Moreover, imipramine activated both extrinsic/intrinsic apoptotic pathways, evidenced by the increased expression of Fas, FasL, cleaved caspase-8, and cleaved caspase-9, along with mitochondrial dysfunction and ROS production. Imipramine inhibited the migration and invasion of bladder cancer cells, likely through the down-regulation of metastasis-related proteins and suppression of the EGFR/ERK/NF-[Formula: see text]B signaling pathway.</p><p><strong>Conclusion: </strong>Imipramine could be a promising therapeutic agent for bladder cancer.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"669-682"},"PeriodicalIF":1.8000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884455/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"In vivo","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/invivo.13871","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background/aim: Bladder cancer is a prevalent malignancy, ranging from superficial forms to more aggressive types that invade the muscle and require extensive treatment. Imipramine, traditionally used as an antidepressant, has shown potential as an anti-cancer agent.
Materials and methods: In this study, human bladder cancer T24 cells were treated with varying concentrations of imipramine to evaluate its cytotoxic and apoptotic effects.
Results: Imipramine induced cytotoxicity in a dose-dependent manner, significantly increasing apoptosis as shown by Annexin-V/PI staining and TUNEL assay. The drug also up-regulated cleaved caspase-3 and down-regulated the anti-apoptotic factor XIAP. Moreover, imipramine activated both extrinsic/intrinsic apoptotic pathways, evidenced by the increased expression of Fas, FasL, cleaved caspase-8, and cleaved caspase-9, along with mitochondrial dysfunction and ROS production. Imipramine inhibited the migration and invasion of bladder cancer cells, likely through the down-regulation of metastasis-related proteins and suppression of the EGFR/ERK/NF-[Formula: see text]B signaling pathway.
Conclusion: Imipramine could be a promising therapeutic agent for bladder cancer.
期刊介绍:
IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management.
The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.