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This work evaluates four selected chalcone thio-derivatives for their effects on NF-κB and STAT3 pathways in human hepatocellular carcinoma cells, linked to inflammation and proliferation. Cell survival was measured in HepG2 and THLE-2 lines, while NF-κB/STAT3 activation and downstream proteins were analyzed by Western blot and qRT-PCR. Proximal kinase phosphorylation was assessed using MagneticBead-Based Multiplex Immunoassay. Derivatives 1 and 5 notably affected viability, cell cycle, apoptosis, and pathway activation with low toxicity to noncancerous cells. Findings support potential use of these synthetic thio-chalcones in molecularly targeted combination therapy for HCC.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/modulatory-effects-of-chalcone-thio-derivatives-on-nf-b-and-stat3-signaling-pathways-in-hepatocellular-carcinoma-cells-a-study-on-selected-active-compounds/331408/",{"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/modulatory-effects-of-chalcone-thio-derivatives-on-nf-b-and-stat3-signaling-pathways-in-hepatocellular-carcinoma-cells-a-study-on-selected-active-compounds/331408.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the purpose of testing the four chalcone thio-derivatives?","Question",{"text":112,"@type":113},"To evaluate their effects on NF-κB and STAT3 signaling pathways involved in inflammatory processes and cell proliferation in human liver cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which cell lines were used to assess cell survival and anticancer effects?",{"text":117,"@type":113},"HepG2 cancer cells and THLE-2 normal cells were used to measure cell survival and related biological outcomes.",{"name":119,"@type":110,"acceptedAnswer":120},"How were NF-κB and STAT3 pathway activation and target gene expression measured?",{"text":121,"@type":113},"NF-κB and STAT3 activation and controlled proteins were assessed using Western blot, while qRT-PCR measured NF-κB and STAT3 target gene expression.","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},331408,1790140083,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31,"preview_page_count":4},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Article  \nModulatory Effects of Chalcone Thio-Derivatives on NF-κB and STAT3 Signaling Pathways in Hepatocellular Carcinoma Cells: A Study on Selected Active Compounds  \nKatarzyna Papierska 1, *, Eliza Judasz 1, Wiktoria Toni ´nska 1, Maciej Kubicki 2 and Violetta Krajka-Ku´zniak 1  \nCitation: Papierska, K.; Judasz, E.; Toni ´nska, W.; Kubicki, M.;  \nKrajka-Ku´zniak, V. Modulatory Effects of Chalcone Thio-Derivativeson NF-κB and STAT3 Signaling Pathways in Hepatocellular Carcinoma Cells: A Study on Selected Active Compounds. Int. J. Mol. Sci. 2024, 25, 10739. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms251910739](10.3390/ijms251910739)  \nAcademic Editors: Susumu Ohya and Katsuhiko Muraki  \nReceived: 19 August 2024  \nRevised: 29 September 2024  \nAccepted: 3 October 2024  \nPublished: 5 October 2024  \nCopyright: © 2024 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Pozna ´n, Poland; [judasz.eliza@gmail.com](judasz.eliza@gmail.com) (E.J.); [wiktoria.toninska99@gmail.com](wiktoria.toninska99@gmail.com) (W.T.); [vkrajka@ump.edu.pl](vkrajka@ump.edu.pl) (V.K.-K.)  \n2 Faculty of Chemistry, Adam Mickiewicz University in Pozna ´n, Uniwersytetu Pozna ´nskiego 8, 61-712 Pozna ´n, Poland; [maciej.kubicki@amu.edu.pl](maciej.kubicki@amu.edu.pl)  \n* Correspondence: [kpapierska@ump.edu.pl](kpapierska@ump.edu.pl)  \nAbstract: Our previous studies demonstrated the modulatory effects of new synthetic thio-chalcone derivatives in dishes on the Nrf2, NF-κB, and STAT3 signaling pathways in colon cancer cells. This study aimed to evaluate the effect of four selected active chalcone thio-derivatives on the NF-κB and STAT3 signaling pathways involved in inflammatory processes and cell proliferation in human liver cancer cells. Cell survival was assessed for cancer (HepG2) and normal (THLE-2) cell lines. Activation of NF-κB and STAT3 signaling pathways and the expression of proteins controlled by these pathways were estimated by Western blot, and qRT-PCR assessed the expression of NF-κB and STAT3 target genes. We also evaluated the impact on the selected kinases responsible for the phosphorylation of the studied transcription factors by MagneticBead-Based Multiplex Immunoassay. Among the thio-derivatives tested, especially derivatives 1 and 5, there was an impact on cell viability, cell cycle, apoptosis, and activation of NF-κB and STAT3 pathways in hepatocellular carcinoma (HCC), which confirms the possibilities of using them in combinatorial molecular targeted therapy of HCC. The tested synthetic thio-chalcones exhibit anticancer activity by initiating proapoptotic processes in HCC while showing low toxicity to non-cancerous cells. These findings confirm the possibility of using chalcone thio-derivatives in molecularly targeted combination therapy for HCC.  \nKeywords: anakoinosis; apoptosis; p53; TNF-α; STAT3; NF-κB; thio-chalcone derivatives; hepatocellular carcinoma cells  \n1. Introduction  \nLiver cancer is a highly heterogeneous cancer that remains one of the most difficult oncology challenges. Inflammatory mediators, whose activators or targets are transcriptional factors such as Signal Transducer and Activator of Transcription 3 (STAT3), and Nuclear Factor kappa B (NF-κB) play a vital role in the development of carcinogenesis hepatocellular carcinoma (HCC) [1] . In normal cells, the NF-κB is a set of dimeric subunits in the cytoplasm bound to inhibitory IkB proteins. Chronic inflammation is associated with the high incidence of HCC, characterized by increased NF-κB activity and overexpression of genes encoding proteins involved i","cbCaitGvtGQ3TPlL","https://ap.wps.com/l/cbCaitGvtGQ3TPlL","pdf",2021713,"English","# Introduction\n## NF-κB in hepatocellular carcinoma progression\n## STAT3 activation and clinical relevance\n## Rationale for chalcone thio-derivatives","[{\"question\":\"What is the purpose of testing the four chalcone thio-derivatives?\",\"answer\":\"To evaluate their effects on NF-κB and STAT3 signaling pathways involved in inflammatory processes and cell proliferation in human liver cancer cells.\"},{\"question\":\"Which cell lines were used to assess cell survival and anticancer effects?\",\"answer\":\"HepG2 cancer cells and THLE-2 normal cells were used to measure cell survival and related biological outcomes.\"},{\"question\":\"How were NF-κB and STAT3 pathway activation and target gene expression measured?\",\"answer\":\"NF-κB and STAT3 activation and controlled proteins were assessed using Western blot, while qRT-PCR measured NF-κB and STAT3 target gene expression.\"}]","Modulatory Effects of Chalcone Thio-Derivatives on NF-κB and STAT3 Signaling Pathways in Hepatocellular Carcinoma Cells - A Study on Selected Active Compounds | PDF",1789993178]