[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331372-105":59,"doc-detail-331372-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","cytochrome-p450-2j2-is-required-for-the-natural-compound-austocystin-d-to-elicit-cancer-cell-toxicity","Cytochrome P450 2J2 is required for the natural compound austocystin D to elicit cancer cell toxicity","","Austocystin D is a natural compound that triggers DNA damage and growth inhibition in specific cancer cell lines through cytochrome P450 (CYP) monooxygenase activity. Cells with higher sensitivity often show increased CYP2J2 expression, yet CYP2J2’s essential role was unclear. Using depletion and overexpression approaches, the study shows that reducing CYP2J2 alleviates austocystin D sensitivity and DNA damage, whereas increasing CYP2J2 enhances both. Multiomics and genetic analyses identify POR and PGRMC1 as positive CYP regulators and KAT7 as a key factor in CYP2J2 transcription, supporting CYP2J2-dependent metabolism and cytotoxic effects. The findings highlight austocystin D as a potential therapeutic prodrug, especially where CYP2J2 could serve as a biomarker.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cytochrome-p450-2j2-is-required-for-the-natural-compound-austocystin-d-to-elicit-cancer-cell-toxicity/331372/",{"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/cytochrome-p450-2j2-is-required-for-the-natural-compound-austocystin-d-to-elicit-cancer-cell-toxicity/331372.png","ImageObject",300,407,{"name":92,"@type":93},"Rowan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does austocystin D cause cancer cell toxicity?","Question",{"text":112,"@type":113},"Austocystin D induces cytochrome P450 (CYP)-dependent DNA damage and growth inhibition. The compound becomes active after enzymatic metabolism, with the oxygenated form reacting with DNA to trigger damage and suppress growth.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What evidence supports CYP2J2 as essential for austocystin D cytotoxicity?",{"text":117,"@type":113},"CYP2J2 depletion reduces austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression increases them. This functional shift supports CYP2J2’s crucial role in downstream cytotoxic effects.",{"name":119,"@type":110,"acceptedAnswer":120},"Which genes and regulators were linked to austocystin D cytotoxicity?",{"text":121,"@type":113},"Gene and multiomics analyses identified POR and PGRMC1 as positive regulators of CYP activity, and KAT7 as a histone acetyltransferase involved in regulating CYP2J2 transcription.","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},331372,1790198105,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"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},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Received: 12 March 2024 | Revised: 25 June 2024 | Accepted: 4 July 2024  \nDOI: 10. 1111/cas.16289  \nOR I G I NAL ART I C L E  \nCytochrome P450 2J2 is required for the natural compound austocystin D to elicit cancer cell toxicity  \nYukiko Kojima1 | Saki Fujieda1 | Liya Zhou1 | Masahiro Takikawa1 | Kouji Kuramochi1 |  \nToshiki Furuya1 | Ayaka Mizumoto2 | Noritaka Kagaya3 | Teppei Kawahara4 | Kazuo Shin-ya3 | Shingo Dan5  | Akihiro Tomida5 | Fuyuki Ishikawa2  | Mahito Sadaie1,2   \n1Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan  \n2Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan  \n3 National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan  \n4Japan Biological Informatics Consortium (JBIC), Tokyo, Japan  \n5Cancer Chemotherapy Center, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan  \nCorrespondence  \nMahito Sadaie, Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.  \n[Email:](Email: msadaie@rs.tus.ac.jp)[ msadaie@rs.tus.ac.jp](Email: msadaie@rs.tus.ac.jp)  \nFunding information  \nJSPS KAKENHI, Grant/Award Number: JP20K07037; AMED, Grant/Award Number: JP20cm0106113; MEXTKAKENHI, Grant/Award Number:  \nJP19H05655  \nAbstract  \nAustocystin D is a natural compound that induces cytochrome P450 (CYP) monooxygenase-dependent DNA damage and growth inhibition in certain cancer cell lines. Cancer cells exhibiting higher sensitivity to austocystin D often display elevated CYP2J2 expression. However, the essentiality and the role of CYP2J2 for the cytotoxicity of this compound remain unclear. In this study, we demonstrate that CYP2J2 depletion alleviates austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression enhances them. Moreover, the investigation into genes involved inaustocystin D cytotoxicity identified POR and PGRMC1, positive regulators for CYP activity, and KAT7, a histone acetyltransferase. Through genetic manipulation and analysis of multiomics data, we elucidated a role for KAT7 in CYP2J2 transcriptional regulation. These findings strongly suggest that CYP2J2 is crucial for austocystin D metabolism and its subsequent cytotoxic effects. The potential use of austocystin D as a therapeutic prodrug is underscored, particularly in cancers where elevated CYP2J2 expression serves as a biomarker.  \nK E Y WO R D S  \naustocystin D, cytotoxicity, DNA damage, gene expression, knockout screening  \nAbbreviations: ABCB1, ATP-binding cassette subfamily B member 1; ATAC-seq, assay for transposase-accessible chromatin using sequencing; AUC, area under the curve; CCD, charge-coupled device; ChIP-seq, chromatin immunoprecipitation sequencing; CHK1, checkpoint kinase 1; CRISPR, clustered regularly interspaced short palindromic repeats; CYP, cytochrome P450; EETs, epoxyeicosatrienoic acids; FDR, false discovery rate; gRNA, guide RNA; H3K4me3, histone H3 trimethylated at lysine 4; IF, immunofluorescence; ING4/5, inhibitor of growth family member 4/5; JFCR39, Japanese Foundation for Cancer Research 39; KAT7, lysine acetyltransferase 7; KICH, kidney chromophobe; KIRP, kidney renal papillary cell carcinoma; MDR1, multidrug resistance protein 1; PGRMC1, progesterone receptor membrane component 1; POLR2A, RNA polymerase II subunit A; POR, cytochrome p450 oxidoreductase; RNA-seq, RNA sequencing; RPA32, replication protein A 32; sgRNA, single-guide RNA; SNAI1, snail family transcriptional repressor 1; THYM, thymoma; TSS, transcription start site; γ-H2AX, histone H2AX phosphorylated at serine 139.  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.  \n© 2024 The Author(s) . Cancer S","cbCaitAHCfJjOamQ","https://ap.wps.com/l/cbCaitAHCfJjOamQ","pdf",1110410,13,"English","# Abstract\n## Keywords\n## Abbreviations\n# Introduction\n## Austocystin D activation and mechanism","[{\"question\":\"How does austocystin D cause cancer cell toxicity?\",\"answer\":\"Austocystin D induces cytochrome P450 (CYP)-dependent DNA damage and growth inhibition. The compound becomes active after enzymatic metabolism, with the oxygenated form reacting with DNA to trigger damage and suppress growth.\"},{\"question\":\"What evidence supports CYP2J2 as essential for austocystin D cytotoxicity?\",\"answer\":\"CYP2J2 depletion reduces austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression increases them. This functional shift supports CYP2J2’s crucial role in downstream cytotoxic effects.\"},{\"question\":\"Which genes and regulators were linked to austocystin D cytotoxicity?\",\"answer\":\"Gene and multiomics analyses identified POR and PGRMC1 as positive regulators of CYP activity, and KAT7 as a histone acetyltransferase involved in regulating CYP2J2 transcription.\"}]","Cytochrome P450 2J2 is required for the natural compound austocystin D to elicit cancer cell toxicity | PDF",1789992982,33]