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This study assessed the anti-cancer activities of 30 monomers extracted from Morus alba L. in gastrointestinal cancer models. Toxicological evaluation showed that most compounds have some toxicity, mainly immunotoxicity, yet they are not life-threatening under normal conditions. Key monomers including Sanggenol L, Sanggenon C, Kuwanon H, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A exhibited significant anti-cancer effects across colon, pancreatic, and gastric cancers. In gastric cancer cells, the compounds inhibited cell-cycle progression and DNA replication-related gene expression and activated unfolded protein response and endoplasmic reticulum stress, contributing to DNA damage, autophagy, and apoptosis. Moracin P, a 2-arylbenzofuran monomer, induced ER stress and promoted apoptosis in vitro and in vivo, supporting its therapeutic potential for gastrointestinal cancer treatment.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/gastrointestinal-cancer-therapeutics-via-triggering-unfolded-protein-response-and-endoplasmic-reticulum-stress-by-2-arylbenzofuran/330043/",{"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/gastrointestinal-cancer-therapeutics-via-triggering-unfolded-protein-response-and-endoplasmic-reticulum-stress-by-2-arylbenzofuran/330043.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main aim of the study?","Question",{"text":112,"@type":113},"To investigate the anti-cancer activities of monomers extracted from Morus alba L. against gastrointestinal cancers and to explore their underlying mechanism, focusing on ER stress and unfolded protein response.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which compound was highlighted as most active, and what did it do in gastric cancer cells?",{"text":117,"@type":113},"Moracin P, characterized as a 2-arylbenzofuran monomer, induced ER stress and promoted apoptosis in gastric cancer cells, suppressing tumor growth in vitro and in vivo.",{"name":119,"@type":110,"acceptedAnswer":120},"How did the monomers affect tumor cells at the molecular level?",{"text":121,"@type":113},"They inhibited cell-cycle progression and DNA replication-related gene expression, and they induced unfolded protein response and endoplasmic reticulum stress, leading to DNA damage, autophagy, and cell death.","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},330043,1790095239,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Article  \nGastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran  \nKui Zhang 1,†, Xin Hu 1,†, Jingjing Su 1, Dong Li 2, Abhimanyu Thakur 3,*, Vikramsingh Gujar 4 and Hongjuan Cui 1, *  \nCitation: Zhang, K.; Hu, X.; Su, J.; Li, D.; Thakur, A.; Gujar, V.; Cui, H. Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran. Int. J. Mol. Sci. 2024, 25, 999. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25020999](10.3390/ijms25020999)  \nAcademic Editor: Davide Moi  \nReceived: 13 December 2023  \nRevised: 8 January 2024  \nAccepted: 10 January 2024  \nPublished: 13 January 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 State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400715, China  \n2 State Key Laboratory of Resource Insects, Institute of Sericulture and Systems Biology, Southwest University, Chongqing 400715, China  \n3 Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA  \n4 Department of Anatomy and Cell Biology, Okhlahoma State University Center for Health Sciences, Tulsa, OK 74107, USA  \n* Correspondence: [abithakur1211@gmail.com](abithakur1211@gmail.com) (A.T.); [hcui@swu.edu.cn](hcui@swu.edu.cn) (H.C.)† These authors contributed equally to this work.  \nAbstract: Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3′-Geranyl-3-prenyl-5,7,2′,4′-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate significant anti-cancer properties against various gastrointestinal cancers, including colon, pancreatic, and gastric cancers. The anti-cancer mechanism of these chemical components was explored in gastric cancer cells, revealing that they inhibit cell cycle and DNA replicationrelated gene expression, leading to the effective suppression of tumor cell growth. Additionally, they induced unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, potentially resulting in DNA damage, autophagy, and cell death. Moracin P, an active monomer characterized as a 2-arylbenzofuran, was found to induce ER stress and promote apoptosis in gastric cancer cells, confirming its potential to inhibit tumor cell growth in vitro and in vivo. These findings highlight the therapeutic potential of Morus alba L. monomers in gastrointestinal cancers, especially focusing on Moracin P as a potent inducer of ER stress and apoptosis.  \nKeywords: Morus alba L.; anti-cancer bioactive compounds; unfolded protein response (UPR); ER stress; Moracin P; gastrointestinal cancers  \n1. Introduction  \nCancer is a leading cause of death worldwide [1], with gastrointestinal cancers such as colon, pancreatic, and gastric cancer posing significant health threats [2] . Despite the extensive efforts directed toward understanding the pathophysiology of these malignancies and developing therapeutic interventions [3], effective treatments are still lacking, and prognosis remains poor for many patients [4] . Gastrointestinal cancers are a diverse group of malignancies that arise from different sites in the digestive system, each with","cbCaiarCTCA5PuUF","https://ap.wps.com/l/cbCaiarCTCA5PuUF","pdf",8380812,26,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What was the main aim of the study?\",\"answer\":\"To investigate the anti-cancer activities of monomers extracted from Morus alba L. against gastrointestinal cancers and to explore their underlying mechanism, focusing on ER stress and unfolded protein response.\"},{\"question\":\"Which compound was highlighted as most active, and what did it do in gastric cancer cells?\",\"answer\":\"Moracin P, characterized as a 2-arylbenzofuran monomer, induced ER stress and promoted apoptosis in gastric cancer cells, suppressing tumor growth in vitro and in vivo.\"},{\"question\":\"How did the monomers affect tumor cells at the molecular level?\",\"answer\":\"They inhibited cell-cycle progression and DNA replication-related gene expression, and they induced unfolded protein response and endoplasmic reticulum stress, leading to DNA damage, autophagy, and cell death.\"}]","Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran | PDF",1789986677,66]