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Andrographolide (AG) is investigated for a mitochondrial-mediated anticancer mechanism through inhibition of pyruvate dehydrogenase kinase 1 (PDK1) expression in lung cancer cells. AG treatment reduced lung cancer cell viability, suppressed aerobic glycolysis by lowering lactate generation, and decreased PDK1 mRNA and protein in a dose-dependent manner.",{"@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":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/andrographolide-suppresses-aerobic-glycolysis-and-induces-apoptotic-cell-death-by-inhibiting-pyruvate-dehydrogenase-kinase-1-expression/380927/",{"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/andrographolide-suppresses-aerobic-glycolysis-and-induces-apoptotic-cell-death-by-inhibiting-pyruvate-dehydrogenase-kinase-1-expression/380927.png","ImageObject",300,407,{"name":92,"@type":93},"moss~","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main purpose of the study on Andrographolide (AG)?","Question",{"text":112,"@type":113},"To investigate how AG exerts a mitochondrial-mediated anticancer effect in lung cancer cells by inhibiting PDK1 expression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does AG affect aerobic glycolysis in lung cancer cells?",{"text":117,"@type":113},"AG significantly suppresses aerobic glycolysis, including decreased lactate generation, alongside reduced glycolysis-related metabolic activity.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports that AG induces apoptotic cell death?",{"text":121,"@type":113},"Flow cytometry and fluorescence microscopy show apoptotic cell death linked to PARP cleavage, caspase-3 activation, increased reactive oxygen species, and loss of mitochondrial membrane potential.","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},380927,1790295196,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"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":41},962090895452,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","ONCOLOGY REPORTS 49: 72, 2023  \nAndrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression  \nEUN‑SUN YANG 1* , YUNJU DO2* , SE‑YUN CHEON 1 , BOSUNG KIM2 , JIN LING2 , MIN KYOUNG CHO 1 , TAEKYUNG KIM3 , SUNG‑JIN BAE4 and KI‑TAE HA 1,2  \n1Korean Medical Research Center for Healthy Aging and 2Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam 50612; 3Department of Biology Education, Pusan National University, Busan 46241; 4Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, Republic of Korea  \nReceived November 17, 2022; Accepted February 7, 2023  \nDOI: 10. 3892/or.2023.8509  \nAbstract. Metabolic disorder is a major characteristic of cancer cells, and controlling genes involved in metabolic shifts can be an effective strategy for cancer treatment. Andrographolide (AG), a diterpenoid lactone, is widely recognized as a natural anticancer drug due to its ability to inhibit cancer growth. The present study aimed to investigate the mechanism underlying the mitochondrial‑mediated anticancer effect of AG by inhib‑ iting pyruvate dehydrogenase kinase 1 (PDK1) expression in lung cancer cells. Cells were treated with AG and PDK1 mRNA and protein expression was determined using reverse transcription‑quantitative PCR and western blotting, respec‑ tively. As a result, AG significantly inhibited the viability of human lung cancer cells and suppressed aerobic glycolysis by decreasing lactate generation. AG further decreased the PDK1 protein and mRNA levels in a dose‑dependent manner. AG‑induced cell death was assessed by flow cytometry and fluorescence microscopy. AG induced apoptotic cell death that was associated with the cleavage of poly (ADP ribose) polymerase, activation of caspase‑3, and mitochondrial damage, which was associated with an increase in reactive oxygen species and loss of mitochondrial membrane potential. AG‑induced cell death was partially suppressed via PDK1 overexpression in lung cancer cells. Therefore, the anticancer  \nCorrespondence to: Professor Ki‑Tae Ha, Department of Korean Medical Science, School of Korean Medicine, Pusan National University, 49 Busandaehak Road, Yangsan, Gyeongsangnam 50612, Republic of Korea  \nE‑[mail: hagis@pusan.ac.kr](mail: hagis@pusan.ac.kr)[ ](mail: hagis@pusan.ac.kr)*Contributed equally  \nKey words: andrographolide, non‑small cell lung cancer, glycolysis, pyruvate dehydrogenase kinase 1, inhibitor  \neffects ofAG on human lung cancer cells may negatively regu‑ late the expression of PDK1.  \nIntroduction  \nDysregulated cellular metabolism is an emerging hallmark of cancer as it supports cellular proliferation and division via biomass generation (1,2) . The most extensively researched metabolic characteristic of cancer cells is the Warburg effect, which favors glycolysis over oxidative phosphoryla‑ tion (OXPHOS) to generate energy, even in the presence of sufficient oxygen (1) . Genomic analysis has revealed that >70% of all human cancer cases show ubiquitous overexpres‑ sion of glycolytic pathway genes (3,4) . Expression levels of genes involved in glucose metabolism, including enolase 1, hexokinase 2 (HK2), glyceraldehyde‑3‑phosphate dehydro‑ genase (GAPDH), glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase 1 (PDK1), are upregulated in most cancer tissues, and hence, can be used as therapeutic targets (3,5,6) . The metabolic switch is directed by limiting the pyruvate utilization in the mitochondrial tricarboxylic acid (TCA) cycle, which is regulated by various cellular events, including altered growth factor signaling, hypoxic or normoxic activation of hypoxia‑inducible factor 1α (HIF1α), oncogene activation and loss‑of‑function of suppressor genes (5,7) .  \nAndrographolide (AG), a diterpenoid lactone, was first identified in Androgr","cbCaijtJVYh9FrSk","https://ap.wps.com/l/cbCaijtJVYh9FrSk","pdf",4995790,12,"English","# Abstract\n# Introduction\n# Materials and methods","[{\"question\":\"What is the main purpose of the study on Andrographolide (AG)?\",\"answer\":\"To investigate how AG exerts a mitochondrial-mediated anticancer effect in lung cancer cells by inhibiting PDK1 expression.\"},{\"question\":\"How does AG affect aerobic glycolysis in lung cancer cells?\",\"answer\":\"AG significantly suppresses aerobic glycolysis, including decreased lactate generation, alongside reduced glycolysis-related metabolic activity.\"},{\"question\":\"What evidence supports that AG induces apoptotic cell death?\",\"answer\":\"Flow cytometry and fluorescence microscopy show apoptotic cell death linked to PARP cleavage, caspase-3 activation, increased reactive oxygen species, and loss of mitochondrial membrane potential.\"}]","Andrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression | PDF",1790242830]