[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-356456-105":59,"doc-detail-356456-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","pseudolaric-acid-b-promotes-lung-cancer-cells-ferroptosis-depending-on-jnkerk-mediated-upregulation-of-survivin","Pseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin","","Pseudolaric acid B (PAB), a diterpenoid extracted from Pseudolarix amabilis, selectively suppresses lung cancer cell viability and downregulates inhibitor of apoptosis proteins (IAPs). Transcriptomic analysis indicates that PAB triggers ferroptosis, accompanied by enhanced lipid oxidation and increased Fe2+ content, while markedly elevating Survivin. Survivin inhibition abolishes PAB-induced ferroptosis, and pathway assays show strengthened JNK and ERK kinase activities. Suppressing JNK/ERK reverses PAB cytotoxicity and restores Survivin and ferroptosis-related proteins, consistent with xenograft results.",{"@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/pseudolaric-acid-b-promotes-lung-cancer-cells-ferroptosis-depending-on-jnkerk-mediated-upregulation-of-survivin/356456/",{"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/pseudolaric-acid-b-promotes-lung-cancer-cells-ferroptosis-depending-on-jnkerk-mediated-upregulation-of-survivin/356456.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What does Pseudolaric acid B do to lung cancer cells?","Question",{"text":113,"@type":114},"PAB selectively inhibits lung cancer cell viability and promotes ferroptotic cell death. It also downregulates inhibitor of apoptosis proteins while increasing Survivin expression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How is ferroptosis induced according to the study?",{"text":118,"@type":114},"PAB enhances lipid oxidation and increases Fe2+ content, which supports ferroptosis. The effect depends on Survivin, because blocking Survivin abolishes PAB-induced ferroptosis.",{"name":120,"@type":111,"acceptedAnswer":121},"What roles do JNK and ERK play in PAB’s mechanism?",{"text":122,"@type":114},"PAB significantly strengthens JNK and ERK kinase activities. Suppressing JNK/ERK reverses PAB-mediated cytotoxicity, restores Survivin and ferroptosis-related proteins, and supports a JNK/ERK–Survivin-dependent pathway.","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},356456,1790207473,{"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":146},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nPseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin  \nYuqiong Li1,2,4, Changping Yu2,4, Shufeng Yang2, Buqing Sai3, Xin Chen1, Ping Chen2, Huoyan Liu2, Jie Jia2, Yu Zhang2, Ruifen Sun1􀀍 & Shaoqing Shi2􀀍  \nLung cancer is one of the most common malignant tumors worldwide, seriously threatening human health. PAB (pseudolaric acid B), an extract of pseudolarix amabilis, has exhibited notable anticancer properties. Nevertheless, the molecular mechanisms underlying PAB-induced anticancer activities remain controversial in lung cancer especially. Herein we aim to investigate the role of IAPs in PABinduced anticancer effects. PAB selectively inhibits the viability of lung cancer cells and downregulates the expression of IAPs. Transcriptomic analysis suggests that PAB induces lung cancer cells ferroptosis. PAB indeed promotes ferroptotic cell death since PAB enhances lipid oxidation and Fe2+ content. Interestingly, PAB markedly enhances Survivin expression. Suppression of Survivin abolishes  \nPAB-induced ferroptosis. PAB significantly strengthens JNK and ERK kinase activities. We further demonstrate suppression of JNK/ERK reversed PAB-mediated-cytotoxicity, meanwhile restores the expression of Survivin and ferroptosis-related proteins. Consistently, xenograft tumor model results also support that PAB induces ferroptosis through Survivin upregulation. Collectively, we demonstrate PAB induces ferroptosis in lung cancer cells in vivo and in vitro depending on JNK and ERK-mediated Survivin upregulation, providing novel insight for clinical administration of PAB in lung cancer.  \nKeywords Lung cancer, PAB, Ferroptosis, Survivin, MAPKs  \nAbbreviations  \nAMPK adenosine 5’-monophosphate (AMP)-activated protein kinase Bax Bcl2-associated X protein  \nBcl2 B-cell lymphoma 2 CQ chloroquine  \nCDK1 cyclin-dependent kinases  \nc-IAP1 cellular inhibitor of apoptosis 1  \nc-IAP2 cellular inhibitor of apoptosis 2 DFO deferoxamine  \nERK extracellular regulated protein kinases GPX4 glutathione peroxidase 4  \nHSP60 heat shock protein 60  \nIAPs inhibitor of apoptosis proteins  \nIHC immunohistochemistry JNK c-Jun N-terminal kinase  \nKEGG Kyoto Encyclopedia of Genes and Genomes MMP mitochondrial membrane potential MAPKs mitogen-activated protein kinase  \nNAIP NLR family apoptosis inhibitory protein  \n1Department of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, No. 1076th, Yuhua Road, Chenggong, Kunming 650500,Yunnan, China. 2Department of Clinical Research Center, First Affiliated Hospital of Kunming Medical University, No. 295th, Xichang Road, Wuhua, Kunming 650000, Yunnan, China.  \n3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming 650500, Yunnan, China. 4Yuqiong Li and Changping Yu contributed equally to this work. 􀀍 email:  \n[sunruifen@ynucm.edu.cn](sunruifen@ynucm.edu.cn); [sqs621@yeah.net](sqs621@yeah.net)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nNCOA4 NSCLCPAB  \nPARP  \nRCD  \nROSSLC7A11 TCM  \nXIAP 4-HNE  \nnuclear Receptor Coactivator 4 non-small cell lung cancer pseudolaric acid B  \npoly ADP-ribose polymerase  \nnon-apoptotic regulated cell death reactive oxygen species  \nsolute carrier family 7 member 11 traditional Chinese Medicine  \nX-linked inhibitor of apoptosis protein 4-Hydroxynonenal  \nLung cancer continues to be the predominant cause of cancer-related mortality worldwide. NSCLC (non-small cell lung cancer) accounts for more than 85% of all lung cancers. Early-stage lung cancer is difficult to diagnose and predict, while the prognosis for advanced-stage lung cancer is unfavorable1,2. Resistance to immunotherapy and molecularly targeted therapy modality is a substantial challenge in clinical therapy3,4. Hence, alternative anti-tumor agents that are both highly effective and have m","cbCaitUJZB6tofgJ","https://ap.wps.com/l/cbCaitUJZB6tofgJ","pdf",3875316,17,"English","# Introduction\n# Background on PAB and lung cancer\n# Role of IAPs in cancer and therapeutic context\n# Study aims","[{\"question\":\"What does Pseudolaric acid B do to lung cancer cells?\",\"answer\":\"PAB selectively inhibits lung cancer cell viability and promotes ferroptotic cell death. It also downregulates inhibitor of apoptosis proteins while increasing Survivin expression.\"},{\"question\":\"How is ferroptosis induced according to the study?\",\"answer\":\"PAB enhances lipid oxidation and increases Fe2+ content, which supports ferroptosis. The effect depends on Survivin, because blocking Survivin abolishes PAB-induced ferroptosis.\"},{\"question\":\"What roles do JNK and ERK play in PAB’s mechanism?\",\"answer\":\"PAB significantly strengthens JNK and ERK kinase activities. Suppressing JNK/ERK reverses PAB-mediated cytotoxicity, restores Survivin and ferroptosis-related proteins, and supports a JNK/ERK–Survivin-dependent pathway.\"}]","Pseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin | PDF",1790125405,43]