[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-337494-105":59,"doc-detail-337494-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","polyunsaturated-fatty-acids-induced-ferroptosis-suppresses-pancreatic-cancer-growth","Polyunsaturated fatty acids-induced ferroptosis suppresses pancreatic cancer growth","","Polyunsaturated fatty acids can trigger ferroptosis, a lipid-oxidation-driven programmed cell death, offering a therapeutic angle for pancreatic cancer. The study demonstrates that linoleic acid and α-linolenic acid induce ferroptosis-associated cell death with necroptotic-like morphological changes in pancreatic cell lines, increasing lipid peroxidation and RIP3/MLKL signaling, which is blocked by ferroptosis inhibitor ferrostatin-1. In vivo, intraperitoneal treatment suppresses xenograft growth and improves survival, with similar effects partially seen in gemcitabine-resistant cells.",{"@graph":69,"@context":123},[70,84,106],{"@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/polyunsaturated-fatty-acids-induced-ferroptosis-suppresses-pancreatic-cancer-growth/337494/",{"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/polyunsaturated-fatty-acids-induced-ferroptosis-suppresses-pancreatic-cancer-growth/337494.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How do LA and α-linolenic acid affect pancreatic cancer cells in this study?","Question",{"text":113,"@type":114},"Linoleic acid and α-linolenic acid induce cell death in pancreatic cancer cell lines, accompanied by increased lipid peroxidation and activation of RIP3 and MLKL-related signaling changes.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What role does ferrostatin-1 play in the observed anti-cancer effects?",{"text":118,"@type":114},"Ferrostatin-1 negates the LA- and α-linolenic-acid-associated effects, restoring measured outcomes toward control levels, supporting ferroptosis involvement.",{"name":120,"@type":111,"acceptedAnswer":121},"Do these fatty acids work against gemcitabine-resistant pancreatic cancer cells?",{"text":122,"@type":114},"Yes, LA and α-linolenic acid show partial ferroptotic effects in gemcitabine-resistant PK cells, though the impact occurs later than in normal PK cells.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},337494,1790074315,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nPolyunsaturated fatty acids‑induced ferroptosis suppresses pancreatic cancer growth  \nAkane Suda1,2,8, Banlanjo Abdulaziz Umaru2,3,8, Yui Yamamoto2, Hiroki Shima4, Yuriko Saiki5, Yijun Pan1,2,6, Liang Jin1,6, Jiaqi Sun1, Yi Ling Clare Low1, Chitose Suzuki7, Takaaki Abe7, Kazuhiko Igarashi4, Toru Furukawa 5, Yuji Owada2 & Yoshiteru Kagawa1,2*  \nDespite recent advances in science and medical technology, pancreatic cancer remains associated with high mortality rates due to aggressive growth and no early clinical sign as well as the unique resistance to anti‑cancer chemotherapy. Current numerous investigations have suggested that ferroptosis, which is a programed cell death driven by lipid oxidation, is an attractive therapeutic indifferent tumor types including pancreatic cancer. Here, we first demonstrated that linoleic acid (LA) and α‑linolenic acid (αLA) induced cell death with necroptotic morphological change in MIA‑Paca2 and Suit 2 cell lines. LA and αLA increased lipid peroxidation and phosphorylation of RIP3 and MLKLin pancreatic cancers, which were negated by ferroptosis inhibitor, ferrostatin‑1, restoring back to BSA control levels. Similarly, intraperitoneal administration of LA and αLA suppresses the growth of subcutaneously transplanted Suit‑2 cells and ameliorated the decreased survival rate of tumor bearing mice, while co‑administration offerrostatin‑1 with LA and αLA negated the anti‑cancer effect. We also demonstrated that LA and αLA partially showed ferroptotic effects on the gemcitabine‑resistant‑PK cells, although its effect was exerted late compared to treatment on normal‑PK cells. In addition, the trial to validate the importance of double bonds in PUFAs in ferroptosis revealed that AA and EPA hada marked effect offerroptosis on pancreatic cancer cells, but DHA showed mild suppression of cancer proliferation. Furthermore, treatment in other tumor cell lines revealed different sensitivity of PUFA‑ induced ferroptosis; e.g., EPA induced a ferroptotic effect on colorectal adenocarcinoma, but LA or αLA did not. Collectively, these data suggest that PUFAs can have a potential to exert an anti‑cancer effect via ferroptosis in both normal and gemcitabine‑resistant pancreatic cancer.  \nKeywords Pancreatic cancer, Drug resistance, Poly unsaturated fatty acids, Linoleic acid, α-Linolenic acid,  \nFerroptosis  \nAbbreviations  \nAA Arachidonic acid  \nαLA α-Linolenic acid  \nBSA Bovine serum albumin  \nDFX Deferasirox  \nDHA Docosahexaenoic acid EPA Eicosapentaenoic acid  \n1Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia. 2Department of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan. 3Center for Childhood Cancer Research, Nationwide Children’s Hospital, Columbus, OH 43205, USA. 4Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. 5Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan. 6Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia. 7Department of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. 8These authors contributed equally: Akane Suda and Banlanjo Abdulaziz Umaru.*[email: yoshiteru.kagawa@florey.edu.au](email: yoshiteru.kagawa@florey.edu.au)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nFA Fatty acid  \nFBS Fetal bovine serum  \nFSP1 Ferroptosis suppressor protein 1 GPX4 Glutathione peroxidase 4  \nLA Linoleic acid  \nLCFA Long chain fatty acid  \nMLKL Mixed lineage kinase domain-like pseudokinase MUFA Monounsaturated fatty acid  \nOA Oleic acid  \nPUFA Polyunsaturated fatty acid RIP Receptor-interacting protein ROS Reactive oxygen species SA Steari","cbCaidlTFt8d4kZn","https://ap.wps.com/l/cbCaidlTFt8d4kZn","pdf",2903159,16,"English","# Overview\n## Background on pancreatic cancer and treatment limits\n## Ferroptosis and its biological features\n# Experimental findings\n## PUFA-induced cell death in pancreatic cell lines\n## Inhibition by ferroptosis inhibitor ferrostatin-1\n## Effects of LA and αLA in tumor-bearing mice\n## Role of PUFA double bonds and comparison of fatty acids\n## Sensitivity across different tumor cell lines","[{\"question\":\"How do LA and α-linolenic acid affect pancreatic cancer cells in this study?\",\"answer\":\"Linoleic acid and α-linolenic acid induce cell death in pancreatic cancer cell lines, accompanied by increased lipid peroxidation and activation of RIP3 and MLKL-related signaling changes.\"},{\"question\":\"What role does ferrostatin-1 play in the observed anti-cancer effects?\",\"answer\":\"Ferrostatin-1 negates the LA- and α-linolenic-acid-associated effects, restoring measured outcomes toward control levels, supporting ferroptosis involvement.\"},{\"question\":\"Do these fatty acids work against gemcitabine-resistant pancreatic cancer cells?\",\"answer\":\"Yes, LA and α-linolenic acid show partial ferroptotic effects in gemcitabine-resistant PK cells, though the impact occurs later than in normal PK cells.\"}]","Polyunsaturated fatty acids-induced ferroptosis suppresses pancreatic cancer growth | PDF",1790019332]