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Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone from the endophytic fungus Phomopsis asparagi, was investigated for activity against HepG2 and HeLa cells and its mechanism within the Wnt/β-catenin cascade. DD-9 inhibited proliferation dose- and time-dependently, reduced clonality and metastasis-related behaviors, induced apoptosis, and caused G0/G1 arrest. Mechanistic assays showed β-catenin nuclear translocation blockade and decreased transcription of Wnt target genes and proteins (p-GSK3-β, β-catenin, LEF1, Axin1, c-Myc, CyclinD1), alongside increased GSK3-β and stabilized degradation complex, supported by molecular docking.",{"@graph":69,"@context":126},[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/dicerandrol-c-suppresses-proliferation-and-induces-apoptosis-of-hepg2-and-hela-cancer-cells-inhibiting-wnt-catenin-signaling-pathway/337906/",{"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/dicerandrol-c-suppresses-proliferation-and-induces-apoptosis-of-hepg2-and-hela-cancer-cells-inhibiting-wnt-catenin-signaling-pathway/337906.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main goal of this study?","Question",{"text":112,"@type":113},"To evaluate the anti-cancer efficacy of Dicerandrol C (DD-9) on HepG2 and HeLa cells and determine its functional mechanism within the Wnt/β-catenin signaling pathway.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the structure of DD-9 confirmed?",{"text":117,"@type":113},"DD-9 was isolated using column chromatographic methods, and its structure was elucidated using 1D NMR.",{"name":119,"@type":110,"acceptedAnswer":120},"What effects did DD-9 have on HepG2 and HeLa cancer cells?",{"text":121,"@type":113},"DD-9 significantly reduced proliferation in a dose- and time-dependent manner, suppressed clonality and metastasis-related behaviors, induced apoptosis, and arrested the cell cycle at the G0/G1 phase.",{"name":123,"@type":110,"acceptedAnswer":124},"How does DD-9 inhibit the Wnt/β-catenin pathway?",{"text":125,"@type":113},"DD-9 attenuated Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and preventing β-catenin translocation to the nucleus, down-regulating Wnt target genes/proteins while up-regulating GSK3-β to promote β-catenin degradation complex stabilization.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},337906,1790138713,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149},5909877438554,"https://ap-avatar.wpscdn.com/avatar/5600025385ad2bf12a7?_k=1778553567797529272","marine drugs   \nArticle  \nDicerandrol C Suppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells by Inhibiting Wnt/β-Catenin Signaling Pathway  \nDongdong Zhou 1,†, Dandan Chen 1,†, Jingwan Wu 1, Ting Feng 1, Pinghuai Liu 1,2 and Jing Xu 1, *  \nCitation: Zhou, D.; Chen, D.; Wu, J.; Feng, T.; Liu, P.; Xu, J. Dicerandrol CSuppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells by Inhibiting Wnt/β-Catenin Signaling Pathway. Mar. Drugs 2024, 22, 278. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)md22060278  \nAcademic Editor: Xiaoling Lu  \nReceived: 24 May 2024  \nRevised: 10 June 2024  \nAccepted: 12 June 2024  \nPublished: 14 June 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 Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China; [zhoudongdonghf@163.com](zhoudongdonghf@163.com) (D.Z.); [21220856000083@hainanu.edu.cn](21220856000083@hainanu.edu.cn) (D.C.); [20081700110009@hainan.edu.cn](20081700110009@hainan.edu.cn) (J.W.); [20081700210004@hainanu.edu.cn](20081700210004@hainanu.edu.cn) (T.F.); [twlph@163.com](twlph@163.com) (P.L.)  \n2 Research and Utilization on Seaweed Biological Resources Key Laboratory of Haikou, Haikou 570228, China  \n* [Correspondence: happyjing3@163.com](Correspondence: happyjing3@163.com); Tel.: +86-898-6627-9226 † These authors contributed equally to this work.  \nAbstract: Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/β catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose-and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G 0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and abrogating β-catenin translocated to the nucleus; down-regulating the transcription level of β-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-β, β-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-β expression, which indicates that DD-9 stabilized the β-catenin degradation complex, thereby inducing β-catenin degradation and inactivation of the Wnt/β-catenin pathway. The possible interaction between DD-9 and β-catenin and GSK3-β protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-β-m","cbCaictJfQtJfExD","https://ap.wps.com/l/cbCaictJfQtJfExD","pdf",7201694,18,"English","# Abstract\n# Introduction\n## Cancer background and Wnt/β-catenin relevance\n## Liver cancer (HCC) treatment limitations\n## Cervical cancer epidemiology and current prevention limits\n# Materials and Methods\n## DD-9 isolation and structure elucidation (1D NMR)\n## Cellular assays (proliferation, clonality, migration, invasion, apoptosis, cell cycle)\n## Pathway validation (dual luciferase, Western blot, immunofluorescence)\n# Results\n## DD-9 suppresses proliferation and induces apoptosis\n## DD-9 arrests the cell cycle at G0/G1\n## DD-9 attenuates Wnt/β-catenin signaling and target gene/protein expression\n# Discussion\n## Possible DD-9–β-catenin/GSK3-β interaction and mechanistic model\n# Conclusions","[{\"question\":\"What was the main goal of this study?\",\"answer\":\"To evaluate the anti-cancer efficacy of Dicerandrol C (DD-9) on HepG2 and HeLa cells and determine its functional mechanism within the Wnt/β-catenin signaling pathway.\"},{\"question\":\"How was the structure of DD-9 confirmed?\",\"answer\":\"DD-9 was isolated using column chromatographic methods, and its structure was elucidated using 1D NMR.\"},{\"question\":\"What effects did DD-9 have on HepG2 and HeLa cancer cells?\",\"answer\":\"DD-9 significantly reduced proliferation in a dose- and time-dependent manner, suppressed clonality and metastasis-related behaviors, induced apoptosis, and arrested the cell cycle at the G0/G1 phase.\"},{\"question\":\"How does DD-9 inhibit the Wnt/β-catenin pathway?\",\"answer\":\"DD-9 attenuated Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and preventing β-catenin translocation to the nucleus, down-regulating Wnt target genes/proteins while up-regulating GSK3-β to promote β-catenin degradation complex stabilization.\"}]","Dicerandrol C Suppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells - Inhibiting Wnt/β-Catenin Signaling Pathway | PDF",1790021125,45]