Mebendazole induces PINK1/Parkin-mediated mitophagy via regulating mTOR/ULK1 signaling pathway by ROS accumulation deriving from mitochondrial stress in melanom

Mebendazole induces PINK1/Parkin-mediated mitophagy via regulating mTOR/ULK1 signaling pathway by ROS accumulation deriving from mitochondrial stress in melanom | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 25 November 2024 V1 Latest version Share on Mebendazole induces PINK1/Parkin-mediated mitophagy via regulating mTOR/ULK1 signaling pathway by ROS accumulation deriving from mitochondrial stress in melanom Authors : Shuping Yang , Zhi Li , Zhiqiang Zhang , Jiamei Yi , Mingyue Pan , Jing Ma , Chuanshan Xu , … Show All … , Xinyu Zhang , Ji Wang , Duo Yi , Weiling Cao , Guodong Yao , and Peng Zhang [email protected] Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.173253270.09014282/v1 328 views 133 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The development of safe and efficient drugs is urgently needed for clinical melanoma treatment. The repurposing of existing drugs for new clinical indications is an impressive strategy for the development of antitumor drugs. In this study, we embarred on an exploration of mebendazole, a well-established antiparasitic drug, to uncover its potential antimelanoma effect and underlying mechanisms. Our findings revealed that mebendazole possessed alluring antimelanoma activity with good safety profiles both in vitro and in vivo. Specifically, the antimelanoma function of mebendazole is derived from the inhibition of cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), as well as the induction of endogenous apoptosis through reactive oxygen species (ROS)-mediated PI3K/Akt/mTOR pathway. Further studies have demonstrated that mebendazole can induce the accumulation of intracellular ROS driven by activating oxidative stress injury and causing a series of manifestations of mitochondrial functional failure. Successively, mitochondrial stress activated Ca2+-mediated and LKB1-mediated AMPK/mTOR/ULK1 pathway, which could trigger PINK1/Parkin-mediated mitophagy. Notably, the ability of mebendazole to induce apoptosis and inhibit proliferation in melanoma cells was related to the induction of PINK1/Parkin-mediated mitophagy. In summary, the present study revealed that mebendazole exerts attractive antimelanoma effects by acting on mitochondria to regulate ROS-mediated multiple signaling pathways. Supplementary Material File (manuscript.docx) Download 167.72 KB Information & Authors Information Version history V1 Version 1 25 November 2024 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords autophagy cancer pharmacology mitochondria stress Authors Affiliations Shuping Yang The Third Affiliated Hospital of Shenzhen University View all articles by this author Zhi Li The Third Affiliated Hospital of Shenzhen University View all articles by this author Zhiqiang Zhang The Third Affiliated Hospital of Shenzhen University View all articles by this author Jiamei Yi The Third Affiliated Hospital of Shenzhen University View all articles by this author Mingyue Pan The Third Affiliated Hospital of Shenzhen University View all articles by this author Jing Ma South China Hospital Affiliated to Shenzhen University View all articles by this author Chuanshan Xu Guangzhou Medical University View all articles by this author Xinyu Zhang Shantou University Medical College View all articles by this author Ji Wang The Third Affiliated Hospital of Shenzhen University View all articles by this author Duo Yi The Third Affiliated Hospital of Shenzhen University View all articles by this author Weiling Cao The Third Affiliated Hospital of Shenzhen University View all articles by this author Guodong Yao Shenyang Pharmaceutical University View all articles by this author Peng Zhang [email protected] The Third Affiliated Hospital of Shenzhen University View all articles by this author Metrics & Citations Metrics Article Usage 328 views 133 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Shuping Yang, Zhi Li, Zhiqiang Zhang, et al. Mebendazole induces PINK1/Parkin-mediated mitophagy via regulating mTOR/ULK1 signaling pathway by ROS accumulation deriving from mitochondrial stress in melanom. Authorea . 25 November 2024. DOI: https://doi.org/10.22541/au.173253270.09014282/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.173253270.09014282/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a028c6c7b8128e2e',t:'MTc3OTkyNDMwMg=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();