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The study focuses on oncofetal receptor tyrosine kinase ROR1 as a targetable driver for precision therapy. Pentagalloyl glucose (PGG), a plant-derived gallotannin small-molecule inhibitor, modulates ROR1-mediated oncogenic signaling, reduces ROR1 and downstream pathways, and suppresses migration, invasion, and cell-cycle progression in PC3 cells.",{"@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/pentagalloyl-glucose-pgg-exhibits-anti-cancer-activity-against-aggressive-prostate-cancer-by-modulating-the-ror1-mediated-akt-gsk3-pathway/330954/",{"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/pentagalloyl-glucose-pgg-exhibits-anti-cancer-activity-against-aggressive-prostate-cancer-by-modulating-the-ror1-mediated-akt-gsk3-pathway/330954.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is ARneg-AI prostate cancer considered difficult to treat?","Question",{"text":112,"@type":113},"ARneg-AI prostate cancer proliferates and metastasizes aggressively, and it does so without relying on androgen-receptor–mediated activation in the usual way, which limits many standard approaches.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the main hypothesis of the study regarding ROR1?",{"text":117,"@type":113},"ROR1 is proposed as a key oncogenic driver and a promising target in aggressive prostate cancers lacking a targetable androgen receptor.",{"name":119,"@type":110,"acceptedAnswer":120},"How does PGG affect prostate cancer cells in the study?",{"text":121,"@type":113},"PGG is reported to suppress ROR1 and downstream oncogenic pathways in PC3 cells, induce apoptosis, and reduce migration, invasion, and cell-cycle progression; it also shows synergy with docetaxel.","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},330954,1790195251,{"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":24,"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":26,"preview_page_count":4},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","Article  \nPentagalloyl Glucose (PGG) Exhibits Anti-Cancer Activity against Aggressive Prostate Cancer by Modulating the ROR1 Mediated AKT-GSK3β Pathway  \nVignesh Sivaganesh 1,2, Tram M. Ta 1 and Bela Peethambaran 1, *  \nCitation: Sivaganesh, V.; Ta, T.M.; Peethambaran, B. Pentagalloyl Glucose (PGG) Exhibits Anti-Cancer Activity against Aggressive Prostate Cancer by Modulating the ROR1 Mediated AKT-GSK3β Pathway. Int.  \nJ. Mol. Sci. 2024, 25, 7003. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25137003](doi.org/10.3390/ijms25137003)  \nAcademic Editor: Pierre Tennstedt  \nReceived: 9 May 2024  \nRevised: 24 June 2024  \nAccepted: 24 June 2024  \nPublished: 26 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 Department of Biology, Saint Joseph’s University, 600 S 43rd St, Philadelphia, PA 19104, USA; [vs271231@pcom.edu](vs271231@pcom.edu) (V.S.); [tt20802863@sju.edu](tt20802863@sju.edu) (T.M.T.)  \n2 Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, 4170 City Ave, Philadelphia, PA 19131, USA  \n* [Correspondence: bpeethambaran@sju.edu](Correspondence: bpeethambaran@sju.edu)  \nAbstract: Androgen-receptor-negative, androgen-independent (ARneg-AI) prostate cancer aggressively proliferates and metastasizes, which makes treatment difficult. Hence, it is necessary to continue exploring cancer-associated markers, such as oncofetal Receptor Tyrosine Kinase like Orphan Receptor 1 (ROR1), which may serve as a form of targeted prostate cancer therapy. In this study, we identify that Penta-O-galloyl-β-D-glucose (PGG), a plant-derived gallotannin small molecule inhibitor, modulates ROR1-mediated oncogenic signaling and mitigates prostate cancer phenotypes. Results indicate that ROR1 protein levels were elevated in the highly aggressive ARneg-AI PC3 cancer cell line. PGG was selectively cytotoxic to PC3 cells and induced apoptosis of PC3 (IC 50 of 31.64 µM) in comparison to normal prostate epithelial RWPE-1 cells (IC 50 of 74.55 µM) . PGG was found to suppress ROR1 and downstream oncogenic pathways in PC3 cells. These molecular phenomena were corroborated by reduced migration, invasion, and cell cycle progression of PC3 cells. PGG minimally and moderately affected RWPE-1 and ARneg-AI DU145, respectively, which may be due to these cells having lower levels of ROR1 expression in comparison to PC3 cells. Additionally, PGG acted synergistically with the standard chemotherapeutic agent docetaxel to lower the IC 50 of both compounds about five-fold (combination index = 0.402) in PC3 cells. These results suggest that ROR1 is a key oncogenic driver and a promising target in aggressive prostate cancers that lack a targetable androgen receptor. Furthermore, PGG may be a selective and potent anti-cancer agent capable of treating ROR1-expressing prostate cancers.  \nKeywords: ROR1; receptor tyrosine kinase; pentagalloyl glucose; targeted therapy; prostate cancer; castration resistance; oncology; natural small molecule inhibitor  \n1. Introduction  \nProstate cancer has a complex molecular pathway that regulates its progression. Initially, prostate cancer relies on the androgen receptor (AR) to elicit survival and metastasis [1,2] . Hence, clinicians seek to target AR pathways through medications that inhibit the production of testosterone in the testes (androgen deprivation therapy) [1–3] . In androgen deprivation therapy (a form of hormone therapy), testosterone and dihydrotestosterone binding to AR is reduced, thus the androgen receptor cannot translocate to the nucleus, bind to androgen response elements (ARE) in nuclear DNA, and subsequently elicit transcription of growth-promoting genes [1,2] . However","cbCaivsRqXI56kVT","https://ap.wps.com/l/cbCaivsRqXI56kVT","pdf",5293165,24,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"Why is ARneg-AI prostate cancer considered difficult to treat?\",\"answer\":\"ARneg-AI prostate cancer proliferates and metastasizes aggressively, and it does so without relying on androgen-receptor–mediated activation in the usual way, which limits many standard approaches.\"},{\"question\":\"What is the main hypothesis of the study regarding ROR1?\",\"answer\":\"ROR1 is proposed as a key oncogenic driver and a promising target in aggressive prostate cancers lacking a targetable androgen receptor.\"},{\"question\":\"How does PGG affect prostate cancer cells in the study?\",\"answer\":\"PGG is reported to suppress ROR1 and downstream oncogenic pathways in PC3 cells, induce apoptosis, and reduce migration, invasion, and cell-cycle progression; it also shows synergy with docetaxel.\"}]","Pentagalloyl Glucose (PGG) Exhibits Anti-Cancer Activity against Aggressive Prostate Cancer by Modulating the ROR1 Mediated AKT-GSK3β Pathway | PDF",1789990860]