[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-331160-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-331160-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","human-nqo1-as-a-selective-target-for-anticancer-therapeutics-and-tumor-imaging","Human NQO1 as a Selective Target for Anticancer Therapeutics and Tumor Imaging","","Human NAD(P)H-quinone oxidoreductase 1 (HNQO1) is a two-electron reductase antioxidant enzyme whose expression is driven by the NRF2 transcription factor, highly active in the prooxidant environment of human malignancies. Cancers show abundant NQO1 expression (up to 200-fold) while most normal body tissues have barely detectable levels, enabling selective tumor marking. NQO1 promotes futile redox cycling of quinones, consuming NADPH and generating bursts of cytotoxic ROS and H2O2. This has motivated NQO1-centered therapeutic strategies, including catalytic inhibitors, reviewed here, and NQO1 turn-on near-infrared probes that enable imaging, quantitation, and guided cancer surgery with theranostic potential for NQO1-targeted chemotherapy.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/human-nqo1-as-a-selective-target-for-anticancer-therapeutics-and-tumor-imaging/331160/",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/human-nqo1-as-a-selective-target-for-anticancer-therapeutics-and-tumor-imaging/331160.png","ImageObject",300,407,{"name":42,"@type":43},"Oliver","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","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 NQO1 considered a selective target in cancers?","Question",{"text":63,"@type":64},"NQO1 expression is strongly driven by NRF2 in the prooxidant milieu of malignancies, reaching up to 200-fold in cancers while remaining barely detectable in most normal tissues.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does NQO1 contribute to tumor cell killing?",{"text":68,"@type":64},"NQO1 catalyzes futile redox cycling of certain natural and synthetic quinones, consuming NADPH and generating rapid bursts of cytotoxic reactive oxygen species (ROS) and H2O2.",{"name":70,"@type":61,"acceptedAnswer":71},"What imaging approach is enabled by cancer-selective NQO1 expression?",{"text":72,"@type":64},"Engineered NQO1 turn-on small molecule probes remain latent in normal tissues but release intense near-infrared fluorescence after enzymatic cleavage in cancer cells and tumor masses, supporting sensitive visualization and quantitation.","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},331160,1790491267,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",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":107,"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},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","cells  \nReview  \nHuman NQO1 as a Selective Target for Anticancer Therapeuticsand Tumor Imaging  \nA. E. M. Adnan Khan , Viswanath Arutla and Kalkunte S. Srivenugopal *  \nCitation: Khan, A.E.M.A.; Arutla, V.; Srivenugopal, K.S. Human NQO1 as a Selective Target for Anticancer Therapeutics and Tumor Imaging. Cells 2024, 13, 1272. [https://](https://)[ ](https://)[doi.org/10.3390/cells13151272](doi.org/10.3390/cells13151272)  \nAcademic Editor: Alexander  \nE. Kalyuzhny  \nReceived: 22 June 2024  \nRevised: 22 July 2024  \nAccepted: 25 July 2024  \nPublished: 29 July 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/)) .  \nDepartment of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, 1406 Amarillo Research Bldg., Rm. 1102, Amarillo, TX 79106, USA;  \n[aekhan@ttuhsc.edu](aekhan@ttuhsc.edu) (A.E.M.A.K.); [viswanatharutla@gmail.com](viswanatharutla@gmail.com) (V.A.)  \n* Correspondence: [kalkunte.srivenugopal@ttuhsc.edu or ksvenugopal@att.net](kalkunte.srivenugopal@ttuhsc.edu or ksvenugopal@att.net)  \nAbstract: Human NAD(P)H-quinone oxidoreductase1 (HNQO1) is a two-electron reductase antioxidant enzyme whose expression is driven by the NRF2 transcription factor highly active in the prooxidant milieu found in human malignancies. The resulting abundance of NQO1 expression (up to 200-fold) in cancers and a barely detectable expression in body tissues makes it a selective marker of neoplasms. NQO1 can catalyze the repeated futile redox cycling of certain natural and synthetic quinones to their hydroxyquinones, consuming NADPH and generating rapid bursts of cytotoxic reactive oxygen species (ROS) and H 2O2. A greater level of this quinone bioactivation due to elevated NQO1 content has been recognized as a tumor-specific therapeutic strategy, which, however, has not been clinically exploited. We review here the natural and new quinones activated by NQO1, the catalytic inhibitors, and the ensuing cell death mechanisms. Further, the cancer-selective expression of NQO1 has opened excellent opportunities for distinguishing cancer cells/tissues from their normal counterparts. Given this diagnostic, prognostic, and therapeutic importance, we and others have engineered a large number of specific NQO1 turn-on small molecule probes that remain latent but release intense fluorescence groups at near-infrared and other wavelengths, following enzymatic cleavage in cancer cells and tumor masses. This sensitive visualization/quantitation and powerful imaging technology based on NQO1 expression offers promise for guided cancer surgery, and thereagents suggest a theranostic potential for NQO1-targeted chemotherapy.  \nKeywords: antioxidant enzymes; tumor-selective therapies; β-lapachone; futile substrates; theranostic drugs; targeted therapy; tumor imaging; NQO1 turn-on probes; near-infrared fluorophores  \n1. Introduction  \nNAD(P)H:quinone oxidoreductases (NQOs) comprise a group of flavoproteins catalyzing the two-electron reduction of quinones and their derivatives. In mammalian systems, there exist two NQO members: NQO1 and NQO2 . NQO1 utilizes NAD(P)H, while NQO2 employs dihydro nicotinamide riboside (NRH) as the electron donor. Beyond their well-documented role in reducing quinone compounds and inhibiting reactive oxygen species formation, NQOs, particularly NQO1, have multifaceted functions in eliciting anti-inflammatory effects, the direct scavenging of superoxide anion radicals, the stabilization of p53 tumor suppressor protein, cancer therapy, and tumor imaging [1] . NQO1 was first found in rodent livers and was given the name DT-diaphorase [2] . In contrast, the identification and characterizatio","cbCaiitS8zf0IGWR","https://ap.wps.com/l/cbCaiitS8zf0IGWR","pdf",17177867,37,"English","# Introduction\n## NQOs and the NQO1/NQO2 distinction","[{\"question\":\"Why is NQO1 considered a selective target in cancers?\",\"answer\":\"NQO1 expression is strongly driven by NRF2 in the prooxidant milieu of malignancies, reaching up to 200-fold in cancers while remaining barely detectable in most normal tissues.\"},{\"question\":\"How does NQO1 contribute to tumor cell killing?\",\"answer\":\"NQO1 catalyzes futile redox cycling of certain natural and synthetic quinones, consuming NADPH and generating rapid bursts of cytotoxic reactive oxygen species (ROS) and H2O2.\"},{\"question\":\"What imaging approach is enabled by cancer-selective NQO1 expression?\",\"answer\":\"Engineered NQO1 turn-on small molecule probes remain latent in normal tissues but release intense near-infrared fluorescence after enzymatic cleavage in cancer cells and tumor masses, supporting sensitive visualization and quantitation.\"}]","Human NQO1 as a Selective Target for Anticancer Therapeutics and Tumor Imaging | PDF",1789991974,93]