[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382713-105":59,"doc-detail-382713-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","gambogic-acid-inhibits-gastric-cancer-cell-proliferation-through-necroptosis","Gambogic Acid Inhibits Gastric Cancer Cell Proliferation through Necroptosis","","Gambogic acid (GA), a xanthonoid from Garcinia hanburyi, is reported to suppress cancer growth but its role in gastric cancer via necroptosis has been unclear. The study tests whether necroptosis mediates GA’s inhibition of gastric cancer cell proliferation using the RIPK1 inhibitor necrostatin-1 (Nec-1), protein phosphorylation analysis, and functional perturbations including necroptosis inhibitors and PGAM5 knockdown. Results show GA promotes necroptosis signaling and that blocking necroptosis attenuates GA-induced cell death and proliferation suppression, supporting necroptosis as the mechanism.",{"@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/gambogic-acid-inhibits-gastric-cancer-cell-proliferation-through-necroptosis/382713/",{"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/gambogic-acid-inhibits-gastric-cancer-cell-proliferation-through-necroptosis/382713.png","ImageObject",300,407,{"name":92,"@type":93},"วิน","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main question of the study about gambogic acid in gastric cancer?","Question",{"text":113,"@type":114},"Whether GA inhibits gastric cancer cell proliferation by involving necroptosis rather than other cell-death pathways.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How did the researchers test the role of necroptosis?",{"text":118,"@type":114},"They used Nec-1, a RIPK1-specific necroptosis inhibitor, and evaluated GA-induced changes in necroptosis-related protein phosphorylation and interactions, alongside inhibitor treatments and PGAM5 knockdown.",{"name":120,"@type":111,"acceptedAnswer":121},"What conclusion is supported by the reported findings?",{"text":122,"@type":114},"GA inhibits gastric cancer cell proliferation by inducing necroptosis, since blocking necroptosis attenuates GA-induced cell death and growth inhibition.","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},382713,1790678136,{"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":52,"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},2336475104736,"https://ap-avatar.wpscdn.com/avatar/22000c4c5e0e5b17e70?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786591360781797222","Hindawi  \nCanadian Journal of Gastroenterology and Hepatology Volume 2023, Article ID 7532367, 10 pages [https://doi.org/10.1155/2023/7532367](https://doi.org/10.1155/2023/7532367)  \nResearch Article  \nGambogic Acid Inhibits Gastric Cancer Cell Proliferation through Necroptosis  \nShujun Wang , Yiping Wang, Hui Zhu, Miaohui Chen, and Liang Zhang  \nDepartment of Gastroenterology, Afliated Cixi People’s Hospital, Wenzhou Medical University, Ningbo, Zhejiang 315300, China Correspondence should be addressed to Shujun Wang; [wshujun@yahoo.com](wshujun@yahoo.com)  \nReceived 4 October 2022; Revised 6 June 2023; Accepted 5 July 2023; Published 8 August 2023  \nAcademic Editor: Antonio Giovanni Solimando  \nCopyright © 2023 Shujun Wang et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nGambogic acid (GA) is a natural xanthonoid secreted by Garcinia hanburyi tree. It possesses anti-cancer activity in various types of cancers. In gastric cancer, it inhibits cell proliferation through increasing apoptosis. However, whether necroptosis is involved in the GA-induced proliferation inhibited in gastric cancer is unknown. In the present study, we found that RIPK1 specifc inhibitor necrostatin-1 (Nec-1) attenuated GA-induced proliferation inhibition. GA treatment increased the phosphorylation of necroptosis-related proteins, RIPK1, RIPK3, and MLKL, and their interactions to form the necrosome complex. Te efector protein Drp-1 was dephosphorylated by GA treatment. Inhibition of necroptosis by diferent inhibitors and PGAM5 knockdown attenuated GA-induced cell death in gastric cancer cell lines, thereby attenuating GA-caused cell proliferation inhibition. All the data supported the conclusion that GA could inhibit gastric cancer cell proliferation by inducing necroptosis.  \n1. Introduction  \nGambogic acid (GA) is a naturally existing xanthonoid that is presented in the resin secreted by Garcinia hanburyi tree [1] . It has been widely investigated for its therapeutic potential in various types of cancers, such as breast cancer, prostate cancer, lung cancer, pancreatic cancer, osteoblastoma, and gastric cancer [1] . GA plays its anti-cancer role through diferent mechanisms. For example, GA inhibits cancer cell proliferation in melanoma by inducing p66SHC/ROS-p53/Bax mediated apoptosis [2] . In pancreatic cancer, GA treatment could induce autophagy and work with chloroquine to inhibit cancer growth by accumulating reactive oxygen species (ROS) [3] . Te biological processes involved in the anti-cancer activity of GA include apoptosis, autophagy, cell cycle arrest, inhibition of cancer cell invasion, metastasis, and angiogenesis [1], but the whole picture of the underlying mechanisms for GA to inhibit cancer progression remains elusive.  \nNecroptosis is a type of caspase-independent, programmed cell death that has been found to be involved in both pathological and physiological processes [4] . Both intrinsic, such as accumulation of reactive oxygen species  \n(ROS), and extrinsic factors, such as activation of toll-like receptors and TNF receptor superfamily, could induce necroptosis in cells [5, 6] . Necrosome complex, a protein complex formed by receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), mediated the process [4] . In addition, the mitochondrial proteins PGAM5 and Drp-1 function as the efector proteins of necroptosis to induce mitochondria fragmentation [5] .  \nGastric cancer (GC) ranks ffth in terms of incidence among all cancer types all over the world [7] . Despite the advancement of surgical and chemo-radiotherapy, the morbidity and mortality in GC remain high. Tere is an unmet need for new therapies to improve the treatment outcome of GC. Several studies on the function of GA in GC have been reported. For","cbCaiay7d6BHS2c2","https://ap.wps.com/l/cbCaiay7d6BHS2c2","pdf",693348,"English","# Introduction\n## Gambogic acid and its anti-cancer mechanisms\n## Necroptosis and the necrosome pathway\n## Gastric cancer burden and need for new therapies\n## Rationale and hypothesis for necroptosis in GA effects","[{\"question\":\"What is the main question of the study about gambogic acid in gastric cancer?\",\"answer\":\"Whether GA inhibits gastric cancer cell proliferation by involving necroptosis rather than other cell-death pathways.\"},{\"question\":\"How did the researchers test the role of necroptosis?\",\"answer\":\"They used Nec-1, a RIPK1-specific necroptosis inhibitor, and evaluated GA-induced changes in necroptosis-related protein phosphorylation and interactions, alongside inhibitor treatments and PGAM5 knockdown.\"},{\"question\":\"What conclusion is supported by the reported findings?\",\"answer\":\"GA inhibits gastric cancer cell proliferation by inducing necroptosis, since blocking necroptosis attenuates GA-induced cell death and growth inhibition.\"}]","Gambogic Acid Inhibits Gastric Cancer Cell Proliferation through Necroptosis | PDF",1790252048,25]