[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-348986-105":59,"doc-detail-348986-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","pharmacological-inhibition-of-apt2-by-solasonine-promotes-ferroptosis-through-palmitoylation-modulation-in-gallbladder-cancer","Pharmacological Inhibition of APT2 by Solasonine Promotes Ferroptosis Through Palmitoylation Modulation in Gallbladder Cancer","","Gallbladder cancer is a lethal biliary malignancy lacking effective therapies. Solasonine, a bioactive alkaloid from Solanum nigrum L, shows antitumor activity, yet its function in gallbladder cancer and its connection to ferroptosis are unclear. This study evaluates solasonine in vitro and in vivo, using subcutaneous and orthotopic xenografts, ferroptosis assays, and transcriptomic pathway analysis. Solasonine induces ferroptosis by elevating MDA, ROS, and Fe2+ while depleting GSH and suppressing GPX4/SLC7A11.",{"@graph":69,"@context":121},[70,84,104],{"@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/pharmacological-inhibition-of-apt2-by-solasonine-promotes-ferroptosis-through-palmitoylation-modulation-in-gallbladder-cancer/348986/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pharmacological-inhibition-of-apt2-by-solasonine-promotes-ferroptosis-through-palmitoylation-modulation-in-gallbladder-cancer/348986.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What is the main therapeutic effect of solasonine on gallbladder cancer in this study?","Question",{"text":111,"@type":112},"Solasonine suppresses gallbladder cancer progression by triggering ferroptosis in tumor models.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"Which ferroptosis-related markers are used to confirm ferroptosis induction?",{"text":116,"@type":112},"The study measures MDA, GSH, ROS, and Fe2+, and evaluates GPX4 and SLC7A11 by qRT-PCR/Western blot.",{"name":118,"@type":109,"acceptedAnswer":119},"How does solasonine mechanistically target APT2 and influence STAT3 signaling?",{"text":120,"@type":112},"Solasonine directly binds APT2, inhibits its enzymatic activity, and blocks STAT3 depalmitoylation, preventing STAT3 nuclear translocation and thereby reducing ferroptosis inhibitor transcription.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},348986,1790095946,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":138,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":67,"update_tm":142,"read_time":143},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Phytotherapy Research   \n RESEARCH ARTICLE  OPEN ACCESS   \nPharmacological Inhibition of APT2 by Solasonine Promotes Ferroptosis Through Palmitoylation Modulation in Gallbladder Cancer  \nLiu-qing Shi1,2 | Jing-wei Zhao1,2  | Jia-yun Zhu1,2 | Cheng Zhao1,2 | Zi-yi Yang1,2 | Li-jia Pan1,2  | Ben Ma3 | Zheng-yu Chen1,2 | Zi-ying Wang1,2 | Chun-jie Li2 | Shi-lei Liu1,2 | Jia-wei Mei1,2 | Ping Dong1,2  \n1Laboratory of General Surgery and Department of General Surgery, Xinhua Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, Shanghai, China | 2Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China | 3Department of Gastrointestinal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China  \nCorrespondence: Shi-lei Liu ([18817818062@163.com](18817818062@163.com)) | Jia-wei Mei ([steve_mei_mjw@126.com](steve_mei_mjw@126.com)) | Ping Dong ([dongping@xinhuamed.com.cn](dongping@xinhuamed.com.cn))  \nReceived: 26 April 2025 | Revised: 18 August 2025 | Accepted: 21 January 2026  \nKeywords: ferroptosis | gallbladder cancer | palmitoylation | solasonine  \nABSTRACT  \nGallbladder cancer (GBC), the most prevalent and lethal biliary tract malignancy, lacks effective therapeutic strategies. Solasonine (SS), a bioactive steroidal alkaloid derived from Solanum nigrum L, exhibits antitumor activity in multiple cancers, but its role in GBC and association with ferroptosis remains unknown. The purpose of this study is to investigate the therapeutic effects of SS on GBC and its underlying mechanisms using both in vitro and in vivo models. The efficacy was tested in subcutaneous models. Then, the anti-GBC effects of SS were assessed via CCK-8, colony formation, and EdU assays. Biosafety was evaluated using L-2F7 cells and murine serum biomarkers. RNA sequencing identified key pathways, validated by ChIP-qPCR and dualluciferase reporter assays. Ferroptosis induction was confirmed by measuring MDA, GSH, ROS, Fe2+, qRT-PCR/Western blot (GPX4/SLC7A11), and rescue experiments. Direct binding ofSS to APT2 was demonstrated through molecular docking, CETSA, and SPR. The study employed orthotopic xenograft models, transwell assays, and wound healing assays to investigate the effects of SS on the metastasis of GBC. SS triggered ferroptosis in GBC by elevating MDA, ROS, and Fe2+ while depleting GSH and downregulating GPX4/SLC7A11. Mechanistically, SS directly bound APT2, inhibiting its enzymatic activity and blocking STAT3 depalmitoylation. This prevented p-STAT3 nuclear translocation, suppressing transcription of ferroptosis inhibitors GPX4 and SLC7A11. In vivo, SS suppressed tumor growth by subcutaneous and orthotopic models with no systemic toxicity. Our findings reveal SS as a novel APT2-targeted ferroptosis inducer that inhibits GBC progression via inhibiting the depalmitoylation process of STAT3, providing a safe and effective therapeutic candidate for this intractable malignancy.  \n1 | Introduction  \nGBC is the most common malignancy of the biliary tract and ranks sixth among gastrointestinal malignancies (Sung  \net al. 2021; Vuthaluru et al. 2023) . Due to its asymptomatic nature in the early stages (Roa et al. 2022), most patients have progressed to the middle and late stages by the time of diagnosis, resulting in a high mortality rate (Feo et al. 2022) . GBC has  \n\n| Abbreviations: APT2 (LYPLA2), acyl-protein thioesterase 2 (lysophospholipase 2); CETSA, cellular thermal shift assay; DCFH-DA, dichlorodihydrofluoresceindiacetate; Fer-1, ferrostatin-1; GBC, gallbladder cancer; GPX4, glutathione peroxidase 4; GSH, glutathione; IHC, immunohistochemistry; MDA, malondialdehyde; qRT-PCR, quantitative reverse transcription-PCR; ROS, reactive oxygen species; SLC7A11, solute carrier family 7-member 11; SPR, surface plasmon resonance; SS, solasonine; STAT3, signal transducer and activator of transcription 3; WB, western blotting.\u003Cbr>Liu-qing Shi, Jing-wei Zhao, and Jia-yun Zhu contribu","cbCaibYxWD7pbulz","https://ap.wps.com/l/cbCaibYxWD7pbulz","pdf",11208274,"English","# Abstract\n# Introduction\n## Background on gallbladder cancer\n## Rationale for ferroptosis and redox regulation\n## STAT3-related mechanisms","[{\"question\":\"What is the main therapeutic effect of solasonine on gallbladder cancer in this study?\",\"answer\":\"Solasonine suppresses gallbladder cancer progression by triggering ferroptosis in tumor models.\"},{\"question\":\"Which ferroptosis-related markers are used to confirm ferroptosis induction?\",\"answer\":\"The study measures MDA, GSH, ROS, and Fe2+, and evaluates GPX4 and SLC7A11 by qRT-PCR/Western blot.\"},{\"question\":\"How does solasonine mechanistically target APT2 and influence STAT3 signaling?\",\"answer\":\"Solasonine directly binds APT2, inhibits its enzymatic activity, and blocks STAT3 depalmitoylation, preventing STAT3 nuclear translocation and thereby reducing ferroptosis inhibitor transcription.\"}]","Pharmacological Inhibition of APT2 by Solasonine Promotes Ferroptosis Through Palmitoylation Modulation in Gallbladder Cancer | PDF",1790081034,48]