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Identifying agents with reduced toxicity and improved therapeutic efficacy compared with current chemotherapeutics is critical. Piperlongumine, a plant-derived compound explored for anticancer activity, was evaluated for metastatic retinoblastoma. Results show strong inhibition of proliferation in metastatic Y79 cells, increased cell death, and reduced MYCN oncogene expression. Extracellular vesicles from treated cells also suppress target-cell growth.",{"@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/piperlongumine-inhibits-proliferation-and-oncogenic-mycn-expression-in-chemoresistant-metastatic-retinoblastoma-cells-directly-and-through-extracellular-vesicles/377810/",{"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/piperlongumine-inhibits-proliferation-and-oncogenic-mycn-expression-in-chemoresistant-metastatic-retinoblastoma-cells-directly-and-through-extracellular-vesicles/377810.png","ImageObject",300,407,{"name":92,"@type":93},"Ezra","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"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 retinoblastoma patients?","Question",{"text":112,"@type":113},"The study focuses on metastatic retinoblastoma, which is associated with poor prognosis and survival. It also highlights the need for compounds with better efficacy and less toxic side effects than existing chemotherapeutics.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does piperlongumine affect metastatic retinoblastoma Y79 cells?",{"text":117,"@type":113},"Piperlongumine significantly inhibits cell proliferation and increases cell death in metastatic retinoblastoma Y79 cells compared with commonly used retinoblastoma chemotherapeutic drugs. It also reduces MYCN oncogene levels.",{"name":119,"@type":110,"acceptedAnswer":120},"What role do extracellular vesicles play in piperlongumine’s effects?",{"text":121,"@type":113},"Extracellular vesicles derived from piperlongumine-treated Y79 cells contain reduced MYCN transcript cargo. EVs from treated cells reduce growth of recipient non-treated Y79 cells, suggesting systemic anti-cancer effects at a distance.","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},377810,1790452522,{"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":52,"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},1099514068035,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Author Manuscript Author Manuscript Author Manuscript Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Biomed Pharmacother. Author manuscript; available in PMC 2023 May 04. |\n| --- | --- |\n\nPublished in final edited form as:  \nBiomed Pharmacother. 2023 May ; 161: 114554. doi:10.1016/j.biopha.2023.114554 .  \nPiperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles  \nCui Shia,b, Kunhui Huanga,b, John Sotoa, Renuka Sankarana,b, Vrinda Kaliac, Onyekwere Onwumerea,d, Michael Younge, Linda Einbonda, Stephen Redentia,b,d,*  \naLehman College, the City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA  \nbBiochemistry Doctoral Program, The Graduate School, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA  \nc Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY 10032, USA  \ndBiology Doctoral Program, The Graduate School of the City University of New York, 365 5th Avenue, New York, NY 10016, USA  \neThe Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA  \nAbstract  \nOcular retinoblastoma malignancies, which develop into metastatic phenotypes, result in poor prognosis and survival for infant and child patients. To improve the prognosis of metastatic retinoblastoma, it is important to identify novel compounds with less toxic side effects and higher therapeutic efficacy compared to existing chemotherapeutics. Piperlongumine (PL), aneuroprotective, plant-derived compound has been explored for its anticancer activities both in vitro and in vivo. Here, we analyze the potential efficacy of PL for metastatic retinoblastoma cell treatment. Our data reveal that PL treatment significantly inhibits cell proliferation in metastatic retinoblastoma Y79 cells compared to the commonly used retinoblastoma chemotherapeutic drugs carboplatin, etoposide, and vincristine. PL treatment also significantly increases cell death compared to treatment with other chemotherapeutic drugs. PL-induced cell-death signaling was  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \n*Corresponding author at: Lehman College, the City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, [USA. Stephen.Redenti@lehman.cuny.edu](USA. Stephen.Redenti@lehman.cuny.edu) (S. Redenti).  \nCRediT authorship contribution statement  \nCui Shi, Kunhui Huang, John Soto, Renuka Sankaran, Stephen Redenti: Conceptualization, Data curation, Formal analysis. Linda Einbond, Onyekwere Onwumere, Vrinda Kalia, Michael Young, Renuka Sankaran: Scientific design guidance, Manuscript review, Editing. Cui Shi, Kunhui Huang, Renuka Sankaran, Stephen Redenti: Writing − original draft, Figure, Data  \ntable generation. Stephen Redenti: Funding acquisition, Investigation, Methodology, Project administration.  \nAppendix A. Supporting information  \nSupplementary data associated with this article can be found in the online version at doi:10.1016/j.biopha.2023.114554 . Conflict of interest statement  \nThe authors declare that there are no conflicts of interest.  \nAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript  \nShi et al. Page 2  \nassociated with significantly higher caspase 3/7 activities and greater loss of mitochondrial membrane potential. PL was also internalized into Y79 cells with an estimated concentration of 0.310pM and expression analysis revealed reduced MYCN oncogene levels. We next examined extracellular vesicles derived from PL-treated Y79 cells. Extracellular vesicles in other cancers are pro-oncogenic, mediating systemic toxicities via the encapsulation of chemotherapeutic drugs.  \nWithin metastatic Y79 EV samples, an estimated PL concentrat","cbCaihqDust3WTHF","https://ap.wps.com/l/cbCaihqDust3WTHF","pdf",2674274,24,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What problem does the study address in retinoblastoma patients?\",\"answer\":\"The study focuses on metastatic retinoblastoma, which is associated with poor prognosis and survival. It also highlights the need for compounds with better efficacy and less toxic side effects than existing chemotherapeutics.\"},{\"question\":\"How does piperlongumine affect metastatic retinoblastoma Y79 cells?\",\"answer\":\"Piperlongumine significantly inhibits cell proliferation and increases cell death in metastatic retinoblastoma Y79 cells compared with commonly used retinoblastoma chemotherapeutic drugs. It also reduces MYCN oncogene levels.\"},{\"question\":\"What role do extracellular vesicles play in piperlongumine’s effects?\",\"answer\":\"Extracellular vesicles derived from piperlongumine-treated Y79 cells contain reduced MYCN transcript cargo. EVs from treated cells reduce growth of recipient non-treated Y79 cells, suggesting systemic anti-cancer effects at a distance.\"}]","Piperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles | PDF",1790227242]