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Reported in vitro effects depend on high doses or mechanical membrane disruption to deliver botulinum neurotoxin into the cytoplasm. Intoxication of non-neuronal cells is several orders of magnitude less potent than in primary neurons. Findings indicate disrupted cancer progression, with some studies reporting apoptosis, and in vivo data largely show similar effects without disclosed safety issues.",{"@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/the-potential-therapeutic-effects-of-botulinum-neurotoxins-on-neoplastic-cells-a-comprehensive-review-of-in-vitro-and-in-vivo-studies/332400/",{"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/the-potential-therapeutic-effects-of-botulinum-neurotoxins-on-neoplastic-cells-a-comprehensive-review-of-in-vitro-and-in-vivo-studies/332400.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What did the systematic review evaluate regarding botulinum neurotoxins and cancer?","Question",{"text":112,"@type":113},"It assessed published in vitro studies on neoplastic cell lines and in vivo studies on neoplastic tumors, focusing on how botulinum toxins affect cancer cell progression and related outcomes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the review findings describe the mechanism and strength of in vitro effects?",{"text":117,"@type":113},"In vitro effects relied on high doses or mechanical disruption of cell membranes to introduce the neurotoxin into the cytoplasm, with intoxication of non-neuronal cells far less potent than for primary neurons.",{"name":119,"@type":110,"acceptedAnswer":120},"What safety and delivery conclusions were reported in the in vivo and translational evidence?",{"text":121,"@type":113},"No safety issues were disclosed in the in vivo studies, and limited evidence suggested anti-neoplastic potential for clostridium difficile, while new delivery modes were tested to improve in vivo neurotoxin delivery.","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},332400,1790341924,{"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":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","toxins   \nReview  \nThe Potential Therapeutic Effects of Botulinum Neurotoxins on Neoplastic Cells: A Comprehensive Review of In Vitro and In Vivo Studies  \nDelaram Safarpour 1, Fattaneh A. Tavassoli 2 and Bahman Jabbari 3, *  \nCitation: Safarpour, D.; Tavassoli, F.A.; Jabbari, B. The Potential Therapeutic Effects of Botulinum Neurotoxins on Neoplastic Cells:  \nA Comprehensive Review of In Vitro and In Vivo Studies. Toxins 2024, 16, 355. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)toxins16080355  \nReceived: 29 June 2024  \nRevised: 8 August 2024  \nAccepted: 10 August 2024  \nPublished: 13 August 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/)) .  \n1 Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA; [safarpou@ohsu.edu](safarpou@ohsu.edu)  \n2 Department of Pathology, School of Medicine, Yale University, New Haven, CT 06520, USA; [fattaneh.tavassoli@yale.edu](fattaneh.tavassoli@yale.edu)  \n3 Department of Neurology, School of Medicine, Yale University, New Haven, CT 06520, USA  \n* [Correspondence: bahman.jabbari@yale.edu](Correspondence: bahman.jabbari@yale.edu); Tel.: +1-914-482-8542  \nAbstract: A systematic review of the literature found fifteen articles on the effect of a botulinum toxin on neoplastic cell lines and eight articles on in vivo neoplasms. The reported in vitro effects rely on high doses or the mechanical disruption of cell membranes to introduce the botulinum neurotoxin into the cell cytoplasm. The potency of the botulinum neurotoxin to intoxicate non-neuronal cells (even cell lines expressing an appropriate protein receptor) is several orders of magnitude lower compared to that to intoxicate the primary neurons. The data suggest that the botulinum toxin disrupts the progression of cancer cells, with some studies reporting apoptotic effects. A majority of the data in the in vivo studies also showed similar results. No safety issues were disclosed in the in vivo studies. Limited studies have suggested similar anti-neoplastic potential for the clostridium difficile. New modes of delivery have been tested to enhance the in vivo delivery of the botulinum toxin to neoplastic cells. Careful controlled studies are necessary to demonstrate the efficacy and safety of this mode of anti-neoplastic treatment in humans.  \nKeywords: botulinum toxin; botulinm neurotoxin; neoplasm; cancer; cancer cells in vitro; in vivo  \nKey Contribution: This review provides an updated information on the studies that assessed the effect botulinum neurotoxins on cancer cells and neoplastic tumors.  \n1. Introduction  \nBotulinum neurotoxins (BoNTs) are widely used for the treatment of a variety of medical conditions. They are considered the drug of first choice for the treatment of cervical dystonia, blepharospasm, and hemifacial spasm [1] . As an inhibitor of acetylcholine release at the neuromuscular junction resulting in decreased muscle tone, BoNTs are potentially powerful agents for the treatment of disabling spasticity in several medical conditions [2] . Furthermore, via the suppression of several major pain transmitters (substance P, calcitonin gene related peptide, and glutamate) [3], the local injection of these agents has been reported to alleviate recalcitrant local pain in a variety of pain syndromes [4–7] .  \nRecent observations indicate a potential role for botulinum toxin therapy in the management of several cancer-related disorders [8]; these include cancer resection/radiotherapyinduced local pain [9,10], the prevention and treatment of post-esophagostomy esophageal stricture [11,12], post-esophagostomy gastroparesis [13,14], post-parotidectomy and pos","cbCaifUKIjqsyDp4","https://ap.wps.com/l/cbCaifUKIjqsyDp4","pdf",427559,"English","# Introduction\n## Background on botulinum neurotoxins\n## Cancer-related disorders and symptoms\n# Study Design\n## Search strategy and reviewers\n## Inclusion and exclusion criteria\n## Article selection and data presentation\n# Results\n## Number of manuscripts identified\n## Final selected studies","[{\"question\":\"What did the systematic review evaluate regarding botulinum neurotoxins and cancer?\",\"answer\":\"It assessed published in vitro studies on neoplastic cell lines and in vivo studies on neoplastic tumors, focusing on how botulinum toxins affect cancer cell progression and related outcomes.\"},{\"question\":\"How do the review findings describe the mechanism and strength of in vitro effects?\",\"answer\":\"In vitro effects relied on high doses or mechanical disruption of cell membranes to introduce the neurotoxin into the cytoplasm, with intoxication of non-neuronal cells far less potent than for primary neurons.\"},{\"question\":\"What safety and delivery conclusions were reported in the in vivo and translational evidence?\",\"answer\":\"No safety issues were disclosed in the in vivo studies, and limited evidence suggested anti-neoplastic potential for clostridium difficile, while new delivery modes were tested to improve in vivo neurotoxin delivery.\"}]","The Potential Therapeutic Effects of Botulinum Neurotoxins on Neoplastic Cells - A Comprehensive Review of In Vitro and In Vivo Studies | PDF",1789998062,25]