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Untargeted metabolomics compared G7 and R24 GBM 2D monolayers and 3D spheroids under identical culture conditions, revealing vitamin B6 pathway metabolite changes in 3D. Hydralazine-mediated reduction of vitamin B6 levels induced death of 3D GBM spheroids, supporting vitamin B6 pathway inhibition as a novel targeted strategy.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/vitamin-b6-pathway-maintains-glioblastoma-cell-survival-in-3d-spheroid-cultures-research-report/332620/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/vitamin-b6-pathway-maintains-glioblastoma-cell-survival-in-3d-spheroid-cultures-research-report/332620.png","ImageObject",300,407,{"name":42,"@type":43},"Rowan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is vitamin B6 pathway targeting explored in glioblastoma?","Question",{"text":63,"@type":64},"GBM progression involves metabolic reprogramming and relapse after initial treatment. The study shows vitamin B6 pathway-associated metabolites are significantly altered in 3D spheroids, and inhibiting the pathway affects GBM viability, supporting it as a therapeutic target.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the study compare GBM behavior in 2D versus 3D cultures?",{"text":68,"@type":64},"Researchers conducted global, untargeted metabolomics on G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical culture conditions, enabling direct assessment of metabolite-level differences.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does hydralazine play in the findings?",{"text":72,"@type":64},"Hydralazine reduces vitamin B6 levels and pharmacological intervention led to cell death in 3D GBM spheroid cultures, indicating that suppressing the vitamin B6 pathway can be therapeutically effective.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332620,1790619633,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Article  \nVitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures  \nNajla Yussuf Moosa 1, Sara Abdullah Azeem 1,†, John K. Lodge 2, William Cheung 3 and Shafiq Uddin Ahmed 1, *  \nCitation: Moosa, N.Y.; Azeem, S.A.; Lodge, J.K.; Cheung, W.; Ahmed, S.U. Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures. Int. J. Mol. Sci. 2024, 25, 10428. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms251910428](10.3390/ijms251910428)  \nAcademic Editors: Maria Mesuraca and Maria Concetta Faniello  \nReceived: 31 August 2024  \nRevised: 17 September 2024  \nAccepted: 24 September 2024  \nPublished: 27 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 School of Medicine, Murray Health, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK; [najla.moosa@sunderland.ac.uk](najla.moosa@sunderland.ac.uk) (N.Y.M.);  \n[bh22us@research.sunderland.ac.uk](bh22us@research.sunderland.ac.uk) (S.A.A.)  \n2 School of Human Sciences, London Metropolitan University, Tower Building, Holloway Road, London N7 8DB, UK; [j.lodge@londonmet.ac.uk](j.lodge@londonmet.ac.uk)  \n3 Department of Applied Sciences, Northumbria University, Ellison Building, Northumberland Road, Newcastle Upon Tyne NE1 8ST, UK; [william.cheung@northumbria.ac.uk](william.cheung@northumbria.ac.uk)  \n* [Correspondence: shafiq.ahmed@sunderland.ac.uk](Correspondence: shafiq.ahmed@sunderland.ac.uk)  \n† Current address: The Pathology Centre, Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust, Gateshead NE6 6GD, UK.  \nAbstract: Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs.  \nKeywords: glioblastoma; vitamin B6; metabolomics; metabolic pathways; 3D culture  \n1. Introduction  \nGlioblastoma (GBM) is the most common form of primary brain tumour in adults. The World Health Organisation (WHO) classifies GBMs as grade IV astrocytomas. In the absence of treatment, GBM patients survive on average for less than 6 months. However, with an optimum treatment plan consisting of surgery, radiotherapy and concomitant temozolomide chemotherapy, median patient survival is 14–16 months [1] . Nevertheless, GBM remains an incurable cancer, marked by resistance to treatment modalities and poor prognosis. Tumour recurrence is inevitable, and this is thought to be driven by interand-intra-tumoral heterogeneity characterised by a distinct cell population with unique molecular and genetic characteris","cbCain463wYOuL1s","https://ap.wps.com/l/cbCain463wYOuL1s","pdf",7537906,21,"English","# Abstract\n# Keywords\n# Introduction\n## Glioblastoma overview and treatment challenges\n## Metabolic reprogramming and amino acid metabolism\n## Context for vitamin B6 pathway targeting","[{\"question\":\"Why is vitamin B6 pathway targeting explored in glioblastoma?\",\"answer\":\"GBM progression involves metabolic reprogramming and relapse after initial treatment. The study shows vitamin B6 pathway-associated metabolites are significantly altered in 3D spheroids, and inhibiting the pathway affects GBM viability, supporting it as a therapeutic target.\"},{\"question\":\"How did the study compare GBM behavior in 2D versus 3D cultures?\",\"answer\":\"Researchers conducted global, untargeted metabolomics on G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical culture conditions, enabling direct assessment of metabolite-level differences.\"},{\"question\":\"What role does hydralazine play in the findings?\",\"answer\":\"Hydralazine reduces vitamin B6 levels and pharmacological intervention led to cell death in 3D GBM spheroid cultures, indicating that suppressing the vitamin B6 pathway can be therapeutically effective.\"}]","Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures - Research report | PDF",1789998934,53]