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This study evaluates isoliensinine effects on urothelial carcinoma cells using MTT, colony formation, flow cytometry, RNA sequencing, and Western blotting. Isoliensinine suppresses T24 and UMUC3 growth and proliferation, induces apoptotic changes, and RNA-seq links mechanism to apoptosis, cell-cycle control, HIF-1 signaling, TNF signaling, and ferroptosis, confirmed by protein analysis. Results support potential combination strategies to improve bladder cancer treatment.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/isoliensinine-induces-ferroptosis-in-urothelial-carcinoma-cells-via-the-pi3kakthif-1-axis-molecular-evidence-from-next-generation-sequencing/374661/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/isoliensinine-induces-ferroptosis-in-urothelial-carcinoma-cells-via-the-pi3kakthif-1-axis-molecular-evidence-from-next-generation-sequencing/374661.png","ImageObject",300,407,{"name":92,"@type":93},"Terk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main purpose of this study on isoliensinine?","Question",{"text":113,"@type":114},"To determine whether isoliensinine can inhibit urothelial carcinoma (UC) cell growth and clarify the underlying molecular mechanisms.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which experimental approaches were used to evaluate the effects on UC cells?",{"text":118,"@type":114},"The study used MTT assays, colony formation assays, flow cytometry, RNA sequencing, and Western blotting.",{"name":120,"@type":111,"acceptedAnswer":121},"What mechanisms are implicated in isoliensinine-induced anti-cancer effects?",{"text":122,"@type":114},"RNA sequencing and protein validation indicate regulation of apoptosis, cell-cycle activity, HIF-1 signaling, TNF signaling, and ferroptosis, leading to impaired UC cell growth and proliferation.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},374661,1790599806,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1099525198933,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Article  \nIsoliensinine Induces Ferroptosis in Urothelial Carcinoma Cells via the PI3K/AKT/HIF-1α Axis: Molecular Evidence from Next-Generation Sequencing  \nYun-Chen Li 1,†, Hsuan-En Huang 1,†, Chia-Ying Yu 1,2, Ya-Chuan Chang 1,2, Shu-Yu Lin 1, Shao-Chuan Wang 1,2, *,‡ and Wen-Wei Sung 1,2,3, *,‡  \nAcademic Editors: Alfredo  \nBerzal-Herranz and Gill Diamond  \nReceived: 29 May 2025  \nRevised: 26 June 2025  \nAccepted: 2 July 2025  \nPublished: 6 July 2025  \nCitation: Li, Y.-C.; Huang, H.-E.; Yu, C.-Y.; Chang, Y.-C.; Lin, S.-Y.; Wang, S.-C.; Sung, W.-W. Isoliensinine Induces Ferroptosis in Urothelial Carcinoma Cells via the PI3K/AKT/ HIF-1α Axis: Molecular Evidence from Next-Generation Sequencing. Pharmaceuticals 2025, 18, 1008 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ph18071008  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;  \n[1101026@live.csmu.edu.tw](1101026@live.csmu.edu.tw) (Y.-C.L.); [s1001007@gm.csmu.edu.tw](s1001007@gm.csmu.edu.tw) (H.-E.H.); [cyyu2015@gmail.com](cyyu2015@gmail.com) (C.-Y.Y.);  \n[raptor7037@gmail.com](raptor7037@gmail.com) (Y.-C.C.); [y2k222d@gmail.com](y2k222d@gmail.com) (S.-Y.L.)  \n2 Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan  \n3 Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan  \n* [Correspondence: rosenbeck.wang@gmail.com](Correspondence: rosenbeck.wang@gmail.com) (S.-C.W.); [flutewayne@gmail.com](flutewayne@gmail.com) (W.-W.S.)† These authors contributed equally to this work.  \n‡ These authors contributed equally to this work.  \nAbstract  \nBackground: Bladder cancer ranks ninth among the most commonly diagnosed cancers, with urothelial carcinoma (UC) accounting for more than 90% of all cases. Given the high recurrence rate and progression risk of bladder cancer, investigating alternative adjunct therapies is imperative. One potential candidate is isoliensinine, which has shown antitumor potential in various cancers; however, the effectiveness of isoliensinine on UCis largely unknown. Methods: In the present study, the effects of isoliensinine on UC cells were examined in a variety of in vitro experiments, including MTT assays, colony formation assays, flow cytometry assays, RNA sequencing analysis, and Western blotting. Results: The isoliensinine-treated T24 and UMUC3 UC cell lines showed cell growth inhibition and proliferation in the MTT and colony formation assays and an apoptotic effect in the flow cytometry assays. RNA sequencing analysis, performed to explain the underlying mechanisms, revealed a significant regulation of cell functions, including apoptosis, the cell cycle, hypoxia-inducible factor 1 (HIF-1) signaling, tumor necrosis factor (TNF) signaling, and ferroptosis. Subsequent Western blotting results verified all these findings. Conclusions: Overall, our data indicate that isoliensinine inhibits UC cell growth and proliferation by inducing apoptosis through alterations in the TNF and HIF1 pathways and ferroptosis. Overall, isoliensinine shows potential for use in new or combined adjunct therapies for the treatment of bladder cancer.  \nKeywords: isoliensinine; ferroptosis; RNA sequencing; bladder cancer; bisbenzylisoquinoline alkaloid  \n1. Introduction  \nBladder cancer, the ninth most frequently diagnosed cancer, is one of the most significant health concerns in developed countries, with approximately 614,000 new cases occurring worldwide in 2022 [1] . Among all bladder cancer cases, urothelial carcinoma (UC) constitutes more than 90% of all diagnoses [2] . Bladder cancers can be classified into non-muscle-invasi","cbCaiu1kr0tfLvTf","https://ap.wps.com/l/cbCaiu1kr0tfLvTf","pdf",2129359,15,"English","# Abstract\n# 1. Introduction\n## Bladder cancer burden and current treatments\n## Rationale for isoliensinine and proposed mechanisms","[{\"question\":\"What is the main purpose of this study on isoliensinine?\",\"answer\":\"To determine whether isoliensinine can inhibit urothelial carcinoma (UC) cell growth and clarify the underlying molecular mechanisms.\"},{\"question\":\"Which experimental approaches were used to evaluate the effects on UC cells?\",\"answer\":\"The study used MTT assays, colony formation assays, flow cytometry, RNA sequencing, and Western blotting.\"},{\"question\":\"What mechanisms are implicated in isoliensinine-induced anti-cancer effects?\",\"answer\":\"RNA sequencing and protein validation indicate regulation of apoptosis, cell-cycle activity, HIF-1 signaling, TNF signaling, and ferroptosis, leading to impaired UC cell growth and proliferation.\"}]","Isoliensinine Induces Ferroptosis in Urothelial Carcinoma Cells via the PI3K/AKT/HIF-1α Axis - Molecular Evidence from Next-Generation Sequencing | PDF",1790202115,38]