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This study evaluates punicic acid (PunA), an age-related free fatty acid, comparing its effects on ovarian cancer versus normal cells and contrasting activity with α-eleostearic acid (α-ESA). PunA selectively impairs ovarian cancer viability while sparing normal cells, enhances cisplatin efficacy, and induces ferroptosis via distinct modulation of lipid peroxidation, fatty acid oxidation, mitochondrial function, and oxidative-stress/ferroptosis pathways. Results are supported by preliminary mouse model data.",{"@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/punicic-acid-in-ovarian-cancer-anticancer-activity-and-mechanistic-insights/354164/",{"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/punicic-acid-in-ovarian-cancer-anticancer-activity-and-mechanistic-insights/354164.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does punicic acid affect ovarian cancer cells compared with normal cells?","Question",{"text":112,"@type":113},"Punicic acid shows greater cytotoxicity in ovarian cancer cells than in normal cells, selectively impairing ovarian cancer cell viability while sparing normal cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What mechanism underlies punicic acid’s anticancer effects?",{"text":117,"@type":113},"Punicic acid induces ferroptosis in ovarian cancer cells and differentially modulates lipid peroxidation, fatty acid oxidation, and mitochondrial function, along with oxidative stress and ferroptosis-associated pathways.",{"name":119,"@type":110,"acceptedAnswer":120},"How does punicic acid interact with cisplatin and what is the potential benefit?",{"text":121,"@type":113},"Punicic acid enhances cisplatin efficacy, suggesting combination therapy may allow lower cisplatin doses while maintaining or improving antitumor activity and improving clinical tolerability.","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},354164,1790168286,{"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":8,"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},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","Article  \nPunicic Acid in Ovarian Cancer: Anticancer Activity and Mechanistic Insights  \nJingjia Mo 1,2,†, Isabella Mendieta 1,†, Alexander J. Adams 1, Katherine Wiest 1, Hannah Lee 1, Victoria Gorman 1, Rachel Koo 1, Santiago Garcia 1, Ethan Nguyen 1, Aaron Lee 1, Jihua Feng 1,3 and Zhiqing Huang 1, *  \nAcademic Editor: AmalM. El-Naggar  \nReceived: 4 February 2026  \nRevised: 21 April 2026  \nAccepted: 22 April 2026  \nPublished: 27 April 2026  \nCopyright: © 2026 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.  \n1 Division of Reproductive Sciences, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC 27701, USA; [mojingjia@sr.gxmu.edu.cn](mojingjia@sr.gxmu.edu.cn) (J.M.); [bella.mendieta@duke.edu](bella.mendieta@duke.edu) (I.M.); [aj.adams@duke.edu](aj.adams@duke.edu) (A.J.A.); [katherine.wiest@duke.edu](katherine.wiest@duke.edu) (K.W.); [hannah.lee@duke.edu](hannah.lee@duke.edu) (H.L.); [vicky.gorman@duke.edu](vicky.gorman@duke.edu) (V.G.); [rachel.koo@duke.edu](rachel.koo@duke.edu) (R.K.); [santiago.garcia@duke.edu](santiago.garcia@duke.edu) (S.G.); [ethan.nguyen@duke.edu](ethan.nguyen@duke.edu) (E.N.); [alee98@bu.edu](alee98@bu.edu) (A.L.); [fengjihua@gxmu.edu.cn](fengjihua@gxmu.edu.cn) (J.F.)  \n2 Department of General Practice, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China  \n3 Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China  \n* Correspondence: [zhiqing.huang@duke.edu](zhiqing.huang@duke.edu); Tel.: +1-919-684-1396 † These authors contributed equally to this work.  \nHighlights  \nWhat are the main findings?  \n• Punicic acid shows greater cytotoxicity in ovarian cancer cells than in normal cells and may enhance the effects of cisplatin.  \n• Punicic Acid induces ferroptosis, alters lipid metabolism, modulates mitochondrial function, and reprograms redox and ferroptosis-associated pathways in ovarian cancer cells.  \nWhat are the implications of the main findings?  \n• This study suggests that combining punicic acid with cisplatin may allow lower chemotherapy doses while maintaining or enhancing antitumor efficacy, potentially improving clinical tolerability.  \n• These findings propose mechanisms that may underly punicic acid’s preferential toxicity, providing insight into ovarian cancer cell vulnerabilities.  \nAbstract  \nOvarian cancer (OC) remains the deadliest gynecological malignancy, with aged tumor microenvironments linked to poorer outcomes. Our prior work identified reduced levels of free fatty acids (FFAs) within tumor-surrounding adipose tissue of aged OC xenograft rats compared to younger counterparts. In this study, we investigated the therapeutic potential of one such FFA, punicic acid (PunA) . We evaluated PunA’s effects on OC and normal cell viability and compared its activity with that of its structural isomer, α-eleostearic acid (α-ESA) . Both compounds decreased OC cell viability; however, α-ESA was cytotoxic to normal cells, whereas PunA selectively impaired OC cell viability while sparing normal cells. Additionally, PunA enhanced cisplatin efficacy, demonstrating its potential for use in combination therapy to reduce cisplatin dosage and toxicity without compromising antitumor activity. Mechanistically, PunA induced ferroptosis in OC cells while sparing normal cells by differently modulating lipid peroxidation, fatty acid oxidation, and mitochondrial function. Transcriptomic profiling further revealed coordinated gene expression changes  \nassociated with oxidative stress and ferroptosis in PunA-treated OC and normal cells. In a preliminary C57BL/6J-ID8 OC mouse model, PunA suppressed tumor growth. Collectively, these findings identify PunA as a promising therapeutic candidate for OC, acting through ferroptosis and mitochondrial dysfunction, and ","cbCaimBz2y8VhL6r","https://ap.wps.com/l/cbCaimBz2y8VhL6r","pdf",16842773,31,"English","# Highlights\n## Main findings\n## Implications of main findings\n# Abstract\n# Keywords\n# 1. Introduction\n## Disease burden and age-related progression\n## Tumor microenvironment and adipose contribution","[{\"question\":\"How does punicic acid affect ovarian cancer cells compared with normal cells?\",\"answer\":\"Punicic acid shows greater cytotoxicity in ovarian cancer cells than in normal cells, selectively impairing ovarian cancer cell viability while sparing normal cells.\"},{\"question\":\"What mechanism underlies punicic acid’s anticancer effects?\",\"answer\":\"Punicic acid induces ferroptosis in ovarian cancer cells and differentially modulates lipid peroxidation, fatty acid oxidation, and mitochondrial function, along with oxidative stress and ferroptosis-associated pathways.\"},{\"question\":\"How does punicic acid interact with cisplatin and what is the potential benefit?\",\"answer\":\"Punicic acid enhances cisplatin efficacy, suggesting combination therapy may allow lower cisplatin doses while maintaining or improving antitumor activity and improving clinical tolerability.\"}]","Punicic Acid in Ovarian Cancer - Anticancer Activity and Mechanistic Insights | PDF",1790109308,78]