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Ceramide, a signaling sphingolipid, was studied as a contributor to stress-induced apoptosis and cell-cycle arrest. The research examined HCT116 colon cancer cells under hypoxia with or without p53 to test whether ceramide metabolism modulation can sensitize p53-deficient cells to hypoxia-induced death.",{"@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/targeting-ceramide-metabolism-to-restore-hypoxia-induced-apoptosis-in-p53-deficient-colon-cancer-cells/444998/",{"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/targeting-ceramide-metabolism-to-restore-hypoxia-induced-apoptosis-in-p53-deficient-colon-cancer-cells/444998.png","ImageObject",300,407,{"name":92,"@type":93},"kopisore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",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 biological problem addressed in the study?","Question",{"text":112,"@type":113},"The study focuses on how hypoxia affects apoptosis and tumor aggressiveness, particularly when p53 is deficient.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does ceramide metabolism relate to hypoxia-induced apoptosis?",{"text":117,"@type":113},"The work proposes that ceramide, as a sphingolipid signaling molecule, influences the balance of pro- and anti-apoptotic outcomes under hypoxic stress.",{"name":119,"@type":110,"acceptedAnswer":120},"What interventions were tested to overcome resistance in p53-deficient cells?",{"text":121,"@type":113},"The study tested shifting sphingolipid balance toward pro-apoptotic species by adding C6 ceramide or sphingosine, or by pharmacologically inhibiting DEGS1 and sphingosine kinase 1.","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},444998,1790822785,{"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":145,"preview_page_count":4},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","OPEN ACCESS  \nCitation: Mechleb K, Hourani N, Fakhry M, Alyamani OA, Hage-Sleiman R, Younes H, et al. (2026) Targeting ceramide metabolism to restore hypoxia-induced apoptosis in p53-deficient colon cancer cells. PLoS One 21(1): e0340295. [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pone.0340295  \nEditor: Herve Le Stunff, Universite Paris Diderot-Paris7-Batiment des Grands Moulins, FRANCE  \nReceived: October 15, 2025  \nAccepted: December 18, 2025  \nPublished: January 6, 2026  \nCopyright: © 2026 Mechleb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nData availability statement: All relevant data are within the manuscript and its Supporting  Information files.  \nFunding: The study was only supported by the Medical Practice Plan (MPP) and the University  \nRESEARCH ARTICLE  \nTargeting ceramide metabolism to restore hypoxia-induced apoptosis in p53-deficient colon cancer cells  \nKaren Mechleb1,2☯, Nancy Hourani1,3☯, Maya Fakhry1, Osama A. Alyamani4,5, Rouba Hage-Sleiman6, Hicham Younes1,6, Antoine Abou Fayad7, Nadia Soudani8,  \nAmer Sakr4, Nadine Darwiche1, Georges Nemer9, Raya Saab10, Marguerite Mrad1,11*, Ghassan Dbaibo1,3*  \n1 Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon, 2 Department of Louvain, Institute of Biomolecular Science and Technology, Faculty of Sciences, Catholic University of Louvain, Louvain, Belgium, 3 Department of Pediatrics and Adolescent Medicine, Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon, 4 Department of Toxicology, Toxicology Lab Research and Training Center, Faculty of Health Sciences, American University of Science & Technology (AUST), Beirut, Lebanon, 5 Forensic Toxicology Laboratory, Center of Forensic & Digital Sciences, Abu Dhabi Judicial Department (ADJD), United Arab Emirates, 6 Department of Biology, Faculty of Sciences, Lebanese University, Hadath, Lebanon, 7 Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon, 8 Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America, 9 Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar,  \n10 Department of Pediatrics, Division of Hematology/Oncology, Stanford University, Stanford, California, United States of America, 11 Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, United States of America  \n☯ These authors contributed equally to this work.  \n* [mrad@wustl.edu](mrad@wustl.edu) (MM); [gdbaibo@aub.edu.lb](gdbaibo@aub.edu.lb) (GD)  \nAbstract  \nHypoxic stress in solid tumors triggers growth arrest and apoptosis through p53 activation and stabilization. This environment inactivates p53 and drives the expansion of p53-mutant clones, which accentuate tumor aggressiveness. Ceramide, a signaling sphingolipid, was previously identified as a downstream collaborator with p53 in the stress-induced apoptosis and cell cycle arrest. Among sphingolipids, the balance between pro-and anti-apoptotic products, dictated by the expression and activity of appropriate enzymes, helps determine cell fate in response to hypoxia. The current study aimed to understand the role of ceramide in HCT116 human colon cancer cells response to hypoxia in the presence or absence of p53, and to determine whether the modulation of ceramide metabolism could sensitize the resistant p53-deficient cells to hypoxia-induced cell death. We observed that HCT116 p53-  \ndeficient cells were resistant to hypoxic cell death. We explored the role of c","cbCaigGEAfVDRI1E","https://ap.wps.com/l/cbCaigGEAfVDRI1E","pdf",1830278,18,"English","# Abstract\n## Introduction\n## Methods and Experimental Approach\n## Findings and Implications","[{\"question\":\"What is the main biological problem addressed in the study?\",\"answer\":\"The study focuses on how hypoxia affects apoptosis and tumor aggressiveness, particularly when p53 is deficient.\"},{\"question\":\"How does ceramide metabolism relate to hypoxia-induced apoptosis?\",\"answer\":\"The work proposes that ceramide, as a sphingolipid signaling molecule, influences the balance of pro- and anti-apoptotic outcomes under hypoxic stress.\"},{\"question\":\"What interventions were tested to overcome resistance in p53-deficient cells?\",\"answer\":\"The study tested shifting sphingolipid balance toward pro-apoptotic species by adding C6 ceramide or sphingosine, or by pharmacologically inhibiting DEGS1 and sphingosine kinase 1.\"}]","Targeting ceramide metabolism to restore hypoxia-induced apoptosis in p53-deficient colon cancer cells | PDF",1790710006,45]