Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy

Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy Aaliya Taiyab, Shaista Haider, Arunabh Choudhury, Aanchal Rathi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4365362/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The increased metabolic activity in cancer cells often leads to higher levels of reactive oxygen species (ROS) compared to normal cells, which can cause damage to cellular components, including DNA. Cancer cells rely on MTH1 to maintain their DNA integrity and cellular function to counteract this damage. MTH1 is critical in sanitizing oxidized nucleotide pools by removing damaged nucleotides. Inhibition of MTH1 disrupts this repair process, leading to increased DNA damage and cell death in cancer cells. In this study, we present resveratrol (RV) as a potential MTH1 inhibitor. Docking and MD Simulations illustrated the effective binding of RV to the active site of the MTH1 protein, forming a notably stable complex. The fluorescence binding studies estimated a high binding affinity of RV with MTH1 ( K a − 6.2 x 10 5 ), inhibiting MTH1 activity with IC 50 20.4µM. The inhibitory effects of RV on the proliferation of breast cancer cells revealed significant inhibition in cell growth, leading to apoptosis. RV significantly increases ROS production, inducing considerable oxidative stress and ultimately resulting in cell death. Our study offers a rationale for evaluating RV as an MTH1 inhibitor for potential anti-cancer therapy, particularly in breast cancer. Natural products MTH1 protein Resveratrol cancer therapy drug discovery MD simulations Full Text Additional Declarations No competing interests reported. Supplementary Files supplementary.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4365362","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298579367,"identity":"681c9369-f445-4ec2-802f-fe4d4ad4fb29","order_by":0,"name":"Aaliya Taiyab","email":"","orcid":"","institution":"Jamia Millia Islamia","correspondingAuthor":false,"prefix":"","firstName":"Aaliya","middleName":"","lastName":"Taiyab","suffix":""},{"id":298579369,"identity":"87bd74d3-05f7-451e-81e0-fdc48ae0faec","order_by":1,"name":"Shaista Haider","email":"","orcid":"","institution":"Shiv Nadar Institution of Eminence Deemed to be University","correspondingAuthor":false,"prefix":"","firstName":"Shaista","middleName":"","lastName":"Haider","suffix":""},{"id":298579371,"identity":"108d5615-58bd-40fa-ab1d-a6b366cc96dc","order_by":2,"name":"Arunabh Choudhury","email":"","orcid":"","institution":"Jamia Millia Islamia","correspondingAuthor":false,"prefix":"","firstName":"Arunabh","middleName":"","lastName":"Choudhury","suffix":""},{"id":298579373,"identity":"18ba5f33-a183-465e-abe1-a1b228f1c6d2","order_by":3,"name":"Aanchal Rathi","email":"","orcid":"","institution":"Jamia Millia Islamia","correspondingAuthor":false,"prefix":"","firstName":"Aanchal","middleName":"","lastName":"Rathi","suffix":""},{"id":298579375,"identity":"d90031e3-0761-4434-a133-f1cef1d2d31d","order_by":4,"name":"Afzal Hussain","email":"","orcid":"","institution":"King Saud University","correspondingAuthor":false,"prefix":"","firstName":"Afzal","middleName":"","lastName":"Hussain","suffix":""},{"id":298579377,"identity":"7e8bdd54-8440-4e93-8c77-333a4e03207a","order_by":5,"name":"Mohamed F Alajmi","email":"","orcid":"","institution":"King Saud University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"F","lastName":"Alajmi","suffix":""},{"id":298579379,"identity":"b365a56d-a82f-4008-a04c-8d124a95d0d1","order_by":6,"name":"Anindita Chakrabarty","email":"","orcid":"","institution":"Shiv Nadar Institution of Eminence Deemed to be University","correspondingAuthor":false,"prefix":"","firstName":"Anindita","middleName":"","lastName":"Chakrabarty","suffix":""},{"id":298579380,"identity":"3cba26eb-6751-4add-9242-d8ac13ea7813","order_by":7,"name":"Asimul Islam","email":"","orcid":"","institution":"Jamia Millia Islamia","correspondingAuthor":false,"prefix":"","firstName":"Asimul","middleName":"","lastName":"Islam","suffix":""},{"id":298579381,"identity":"99502ed9-b09b-49a7-9f24-e79fb607edae","order_by":8,"name":"Md. Imtaiyaz Hassan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDACZh4Izc9wAAiBgI1oLZINRGthgGoxOECsu3TbeQ9+/PHHLs/44OnEAww1dgx80g34tZgd5kuW5m1LLjY7cHbDAYZjyQxsMgTsMzvMYyDN2MCcuA2shQ2IJBIIajH++eNPfeLmBpCWf8RpMZPgYTucuIEBqIWxjUgt1rxtxxNngByW2JfMQ1jL+TPGN3/8qU7sn3F284cP3+zk5GcQ0IIAEgcYGBLg0UQU4G8gQfEoGAWjYBSMKAAAX/lGe1i8t9IAAAAASUVORK5CYII=","orcid":"","institution":"Jamia Millia Islamia","correspondingAuthor":true,"prefix":"","firstName":"Md.","middleName":"Imtaiyaz","lastName":"Hassan","suffix":""}],"badges":[],"createdAt":"2024-05-03 17:24:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4365362/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4365362/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56735579,"identity":"7e85a5b5-af0a-4735-b0af-f2a50122bf1e","added_by":"auto","created_at":"2024-05-19 15:31:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1312153,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptMCBI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4365362/v1_covered_8c3d4a6f-c824-4f44-8ce4-873f92b2e085.pdf"},{"id":56172241,"identity":"17dd3a04-fbbc-44fb-8c43-274ba37c51b6","added_by":"auto","created_at":"2024-05-09 12:05:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3882838,"visible":true,"origin":"","legend":"","description":"","filename":"supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-4365362/v1/e2db249d6c994a54ab847bcd.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Natural products; MTH1 protein; Resveratrol, cancer therapy, drug discovery, MD simulations","lastPublishedDoi":"10.21203/rs.3.rs-4365362/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4365362/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe increased metabolic activity in cancer cells often leads to higher levels of reactive oxygen species (ROS) compared to normal cells, which can cause damage to cellular components, including DNA. Cancer cells rely on MTH1 to maintain their DNA integrity and cellular function to counteract this damage. MTH1 is critical in sanitizing oxidized nucleotide pools by removing damaged nucleotides. Inhibition of MTH1 disrupts this repair process, leading to increased DNA damage and cell death in cancer cells. In this study, we present resveratrol (RV) as a potential MTH1 inhibitor. Docking and MD Simulations illustrated the effective binding of RV to the active site of the MTH1 protein, forming a notably stable complex. The fluorescence binding studies estimated a high binding affinity of RV with MTH1 (\u003cem\u003eK\u003c/em\u003ea \u0026minus;\u0026thinsp;6.2 x 10\u003csup\u003e5\u003c/sup\u003e), inhibiting MTH1 activity with IC\u003csub\u003e50\u003c/sub\u003e 20.4\u0026micro;M. The inhibitory effects of RV on the proliferation of breast cancer cells revealed significant inhibition in cell growth, leading to apoptosis. RV significantly increases ROS production, inducing considerable oxidative stress and ultimately resulting in cell death. Our study offers a rationale for evaluating RV as an MTH1 inhibitor for potential anti-cancer therapy, particularly in breast cancer.\u003c/p\u003e","manuscriptTitle":"Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 12:05:20","doi":"10.21203/rs.3.rs-4365362/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a65f747c-15ad-4ad1-a6d9-230d0cc28863","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-19T15:23:47+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-09 12:05:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4365362","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4365362","identity":"rs-4365362","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}