[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-440119-105":59,"doc-detail-440119-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","identification-of-epigenetic-monotherapy-candidates-in-taxane-resistant-crpc","Identification of epigenetic monotherapy candidates in taxane-resistant CRPC","","Taxane resistance continues to undermine effective therapy for castration-resistant prostate cancer (CRPC). This study uses a small-molecule screening strategy to uncover epigenetic vulnerabilities in two taxane-resistant CRPC cell lines, DU145 and 22Rv1, resistant to docetaxel and cabazitaxel. A targeted epigenetic regulator library was screened for effects on resistant cell viability, followed by clonogenic, apoptosis (Annexin V/PI), and protein/histone mark validation. 4-Iodo-SAHA and SP2509 show strong monotherapy cytotoxicity and target-consistent epigenetic modulation, and they enhance docetaxel activity while helping overcome resistance.",{"@graph":69,"@context":122},[70,84,105],{"@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/identification-of-epigenetic-monotherapy-candidates-in-taxane-resistant-crpc/440119/",{"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/identification-of-epigenetic-monotherapy-candidates-in-taxane-resistant-crpc/440119.png","ImageObject",300,407,{"name":92,"@type":93},"Bulrr","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address in CRPC therapy?","Question",{"text":112,"@type":113},"The study targets the persistent challenge of taxane resistance in castration-resistant prostate cancer, which limits long-term treatment effectiveness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were epigenetic monotherapy candidates identified?",{"text":117,"@type":113},"Researchers screened a small-molecule library against epigenetic regulators using parental and taxane-resistant CRPC cell lines, then validated selected hits with clonogenic assays, Annexin V/PI flow cytometry, and Western blot analysis of histone marks and target proteins.",{"name":119,"@type":110,"acceptedAnswer":120},"Which compounds were highlighted and what evidence supports them?",{"text":121,"@type":113},"4-Iodo-SAHA (HDAC inhibitor) and SP2509 (LSD1 inhibitor) were identified as cytotoxic agents. They induced cell death, impaired long-term survival, increased target-consistent histone marks (H3K27Ac and H3K4me2), and depleted HDAC7 and LSD1 respectively.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},440119,1792658738,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Turkish Journal of Biology  \n\n| Volume 49  Number 7 | Article 4 |\n| --- | --- |\n| 12-29-2025\u003Cbr>Identification of epigenetic monotherapy candidates in taxane-resistant CRPC\u003Cbr>BUSE CEVATEMRE İPEK BULUTEZGİ KARYEMEZ\u003Cbr>CEYDA AÇILAN\u003Cbr>Follow this and additional works at: [https://journals.tubitak.gov.tr/biology](https://journals.tubitak.gov.tr/biology)\u003Cbr> Part of the Biology Commons |  |\n\nRecommended Citation  \nCEVATEMRE, B, BULUT, İ, KARYEMEZ, E, & AÇILAN, C (2025) . Identification of epigenetic monotherapy candidates in taxane-resistant CRPC. Turkish Journal of Biology 49 (7): 757-769 . [https://doi.org/](https://doi.org/)[ ](https://doi.org/)10.55730/1300-0152.2778  \nThis work is licensed under a Creative Commons Attribution 4.0 International License.  \nThis Research Article is brought to you for free and open access by TÜBİTAK Academic Journals. It has been accepted for inclusion in Turkish Journal of Biology by an authorized editor of TÜBİTAK Academic Journals. For more information, please contact [academic.publications@tubitak.gov.tr](academic.publications@tubitak.gov.tr)  \n\n| \u003Cbr>| Turkish Journal of Biology [http://journals.tubitak.gov.tr/biology/](http://journals.tubitak.gov.tr/biology/)\u003Cbr>\u003Cbr>Research Article | Turk J Biol\u003Cbr>(2025) 49: 757-769\u003Cbr>© TÜBİTAK\u003Cbr>doi:10.55730/1300-0152.2778 |\n| --- | --- | --- |\n\nIdentification of epigenetic monotherapy candidates in taxane-resistant CRPC  \nBuse CEVATEMRE1,2,*􀁋, İpek BULUT2􀁋, Ezgi KARYEMEZ3􀁋, Ceyda AÇILAN1,2􀁋 1School of Medicine, Koç University, İstanbul, Turkiye 2Research Center for Translational Medicine, Koç University, İstanbul, Turkiye 3Graduate School of Health Sciences, Koç University, İstanbul, Turkiye  \nReceived: 14.05.2025  Accepted/Published Online: 05.11.2025  Final Version: 29.12.2025  \nBackground/aim: Taxane resistance remains a significant challenge in the effective treatment of castration-resistant prostate cancer (CRPC). Given the association of epigenetic regulation with chemotherapy resistance and cancer progression, this study aims to identify epigenetic vulnerabilities in two CRPC cell lines (DU145 and 22Rv1) established as resistant to two different taxanes, docetaxel (Dtx) and cabazitaxel (Cbz), using a small-molecule screening approach.  \nMaterials and methods: A small-molecule library targeting epigenetic regulators, including histone deacetylases (HDAC), histone methyltransferases, histone demethylases, bromodomain proteins, deoxyribonucleic acid methyltransferases, protein arginine deiminase, and histone acetyltransferase was utilized. Drug screening was performed on parental and taxane-resistant CRPC cell lines. Cell viability was assessed using the sulforhodamine B assay to identify compounds impairing the growth of resistant cells. Selected hits were further evaluated for their impact on colony-forming capacity using clonogenic assays, and cell death was confirmed by Annexin V/PI flow cytometry. Western blotting was used to assess histone modification marks (e.g., H3K27Ac, H3K4me2) and protein targets, including HDAC7 and lysine-specific demethylase 1 (LSD1) . In combination studies, resistant cell lines were exposed to fixed-dose taxanes in combination with selected compounds. Combenefit software was used to generate synergy maps.  \nResults: Screening results revealed that taxane-resistant CRPC cells remained susceptible to multiple epigenetic inhibitors rather thana single dominant class. Among the identified compounds, 4-Iodo-SAHA (HDAC inhibitor) and SP2509 (LSD1 inhibitor) emerged as cytotoxic agents, inducing cell death at levels comparable to those of parental cells. Further validation confirmed their efficacy in impairing cell viability and long-term survival in taxane-resistant CRPC cells, as demonstrated by Annexin V/PI flow cytometry. Both compounds induced epigenetic modulations consistent with their targets, reflected by increased histone marks (H3K27Ac for 4-Iodo-SAHA; H3K4me2 for SP2509), and were also associated with deplet","cbCaimEcrQh4s6bC","https://ap.wps.com/l/cbCaimEcrQh4s6bC","pdf",9858223,15,"English","# Background/aim\n# Materials and methods\n## Drug screening and validation\n# Results\n# Conclusion\n# Key words\n# Introduction","[{\"question\":\"What problem does the study address in CRPC therapy?\",\"answer\":\"The study targets the persistent challenge of taxane resistance in castration-resistant prostate cancer, which limits long-term treatment effectiveness.\"},{\"question\":\"How were epigenetic monotherapy candidates identified?\",\"answer\":\"Researchers screened a small-molecule library against epigenetic regulators using parental and taxane-resistant CRPC cell lines, then validated selected hits with clonogenic assays, Annexin V/PI flow cytometry, and Western blot analysis of histone marks and target proteins.\"},{\"question\":\"Which compounds were highlighted and what evidence supports them?\",\"answer\":\"4-Iodo-SAHA (HDAC inhibitor) and SP2509 (LSD1 inhibitor) were identified as cytotoxic agents. They induced cell death, impaired long-term survival, increased target-consistent histone marks (H3K27Ac and H3K4me2), and depleted HDAC7 and LSD1 respectively.\"}]","Identification of epigenetic monotherapy candidates in taxane-resistant CRPC | PDF",1790691209,38]