Pharmacological Inhibition of METTL3 Suppresses Colon Cancer Proliferation, Migration and Cancer Stemness

Pharmacological Inhibition of METTL3 Suppresses Colon Cancer Proliferation, Migration and Cancer Stemness | 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 Pharmacological Inhibition of METTL3 Suppresses Colon Cancer Proliferation, Migration and Cancer Stemness Chandrasudan Ramamurthy, Bavya Chandrasekhar, Yasodha Kesavan, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9461578/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract As one of the most common and deadly cancers in the world, colorectal cancer (CRC) calls for the creation of innovative treatment approaches. Although bonducellin, a naturally occurring flavonoid produced from Caesalpinia bonducella, has shown encouraging anticancer effects, little is known about its molecular mode of action in colorectal cancer. In this work, we examined Bonducellin's potential as an inhibitor of methyltransferase-like 3 (METTL3), a crucial RNA methyltransferase linked to the development of colorectal cancer. According to molecular docking, Bonducellin has a high affinity for the RNA binding pocket of METTL3, which is maintained by hydrophobic and hydrogen bonding interactions. Bonducellin dramatically reduced the migration, colony formation, and proliferation of SW480 and SW620 cells in in vitro tests, with IC 50 values of 43.5 µM and 51.3 µM. Apoptosis induction was validated by acridine orange/ethidium bromide staining, and the anti-angiogenic function of bonducellin was established by the CAM test. All of these results point to Bonducellin's potential as a natural small-molecule lead for CRC therapy by showing that it inhibits METTL3 and induces apoptosis to limit CRC cell proliferation and migration. Bonducellin METTL3 Colorectal cancer Epigenetics Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 20 Apr, 2026 Editor assigned by journal 20 Apr, 2026 Submission checks completed at journal 20 Apr, 2026 First submitted to journal 19 Apr, 2026 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. 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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-9461578","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":630001591,"identity":"6f2cb5d9-a9fa-4742-a729-5e3fcdd8f034","order_by":0,"name":"Chandrasudan Ramamurthy","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Chandrasudan","middleName":"","lastName":"Ramamurthy","suffix":""},{"id":630001592,"identity":"a867c494-802b-40e9-aa40-beeb85886a55","order_by":1,"name":"Bavya Chandrasekhar","email":"","orcid":"","institution":"SRM Institute of Science 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Although bonducellin, a naturally occurring flavonoid produced from Caesalpinia bonducella, has shown encouraging anticancer effects, little is known about its molecular mode of action in colorectal cancer. In this work, we examined Bonducellin's potential as an inhibitor of methyltransferase-like 3 (METTL3), a crucial RNA methyltransferase linked to the development of colorectal cancer. According to molecular docking, Bonducellin has a high affinity for the RNA binding pocket of METTL3, which is maintained by hydrophobic and hydrogen bonding interactions. Bonducellin dramatically reduced the migration, colony formation, and proliferation of SW480 and SW620 cells in in vitro tests, with IC\u003csub\u003e50\u003c/sub\u003e values of 43.5 \u0026micro;M and 51.3 \u0026micro;M. Apoptosis induction was validated by acridine orange/ethidium bromide staining, and the anti-angiogenic function of bonducellin was established by the CAM test. 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