[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332847-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332847-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","unveiling-the-antimetastatic-activity-of-monoterpene-indole-alkaloids-targeting-mmp9-in-cancer-cells","Unveiling the antimetastatic activity of monoterpene indole alkaloids targeting MMP9 in cancer cells","","Distant metastasis and acquired resistance limit chemotherapy and targeted therapy outcomes. The tumor microenvironment shapes whether cancers respond to pharmacological treatments, and matrix metalloproteinase 9 (MMP9) contributes to extracellular matrix breakdown and cancer-cell motility. This study identifies MMP9-targeting monoterpene indole alkaloids (MIAs) and evaluates their effects on cell viability and motility using cell assays, gene and protein analyses, reporter systems, and molecular docking, with pharmacokinetic assessment. MIAs suppressed MMP9-related signaling and regulated migration, invasion, EMT, and immune evasion, supporting antimetastatic potential at safe doses.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/unveiling-the-antimetastatic-activity-of-monoterpene-indole-alkaloids-targeting-mmp9-in-cancer-cells/332847/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/unveiling-the-antimetastatic-activity-of-monoterpene-indole-alkaloids-targeting-mmp9-in-cancer-cells/332847.png","ImageObject",300,407,{"name":42,"@type":43},"Evangeline","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What therapeutic challenge does the study address?","Question",{"text":63,"@type":64},"Distant metastasis and acquired resistance reduce the effectiveness of chemotherapy and molecularly targeted therapies.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which molecular target do the monoterpene indole alkaloids aim to affect?",{"text":68,"@type":64},"They target matrix metalloproteinase 9 (MMP9), which is linked to extracellular matrix degradation and cancer-cell motility.",{"name":70,"@type":61,"acceptedAnswer":71},"How were the antimetastatic effects evaluated?",{"text":72,"@type":64},"The study used assays for cell viability, migration, and invasion, along with qRT-PCR, pathway-focused expression analysis, Western blotting, reporter assays, molecular docking, and target prediction.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332847,1791184515,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":55,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","Molecules and Cells Research Article  \nUnveiling the antimetastatic activity of monoterpene indole alkaloids targeting MMP9 in cancer cells, with a focus on pharmacokinetic and cellular insights  \nMücahit Varlı 1 , Kyungha Lee2 , Kyo Bin Kang2 , and Hangun Kim 1 ,⁎  \n1College of Pharmacy, Sunchon National University, Sunchon 57922, Korea, 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Sookmyung Women’s University, Seoul 04310, Korea  \n⁎Corresponding [author. hangunkim@sunchon.ac.kr](author. hangunkim@sunchon.ac.kr)[ ](author. hangunkim@sunchon.ac.kr)[https://doi.org/10.1016/j.mocell.2024.100143](https://doi.org/10.1016/j.mocell.2024.100143)  \nABSTRACT  \nDistant metastasis, together with acquired resistance, limits the therapeutic impact of chemotherapy and molecularly targeted therapies. The properties of the tumor microenvironment determine how sensitive or resistant various cancers are to specific pharmacological treatments. Matrix metalloproteinase 9 (MMP9) is widely known for its ability to break down the extracellular matrix and it also modulates the motility of cancer cells. Here, our goal was to identify compounds that target MMP9 and evaluate their capacity to inhibit the motility of cancer cells. The antimetastatic effect of monoterpene indole alkaloids (MIAs) on cell viability and motility was evaluated by methyl thiazolyl tetrazolium assay, migration assay, invasion assay, quantitative real-time polymerase chain reaction, pathway-focused expression analysis, Western blotting, reporter assay, molecular docking simulation, and target prediction. MIA compounds target MMP9 . MIAs inhibited the expression of phospho-epidermal growth factor receptor, phospho-Akt, phospho-JNK, and cyclin D1 . Additionally, MIAs had predicted favorable pharmacokinetic profile and drug-like properties. Furthermore, among the MIA compounds, lyaloside and 5(S)-5-carbomethoxystrictosidine had low cytotoxicity and regulated cancer-related signaling, including cell migration, cell invasion, epithelial-mesenchymal transition, and immune evasion. Our findings demonstrated that the MIAs used in this study have potential antimetastasis properties that occur via MMP9-mediated regulation of cancer signaling and have the potential to be used therapeutically at safe doses.  \n© 2024 The Authors. Published by Elsevier Inc. on behalf of Korean Society for Molecular and Cellular Biology. This isan open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)) .  \nKeywords: 5(S)-5-carbomethoxystrictosidine, Anticancer, Lyaloside, Matrix metalloproteinase 9, Monoterpene indole alkaloids  \nINTRODUCTION  \nMany cancer-related deaths are associated with metastasis. Metastasis, which is a distinctive feature of cancer, results from multiple processes (Hanahan and Weinberg, 2011) . These processes include the modeling of the tumor microenvironment, the invasion of tumor cells into the lymph and blood, and their spread via the circulation, then infiltration into tissues, and the development of a new microenvironment (Lambert et al. , 2017; Owyong et al. , 2019) . The extracellular matrix (ECM) is an important component of the tumor microenvironment. Physical and chemical environmental conditions, such as the presence of collagen and fibronectin, provide conditions that are vital for tumor cell survival (Kessenbrock et al. , 2010; Tzanakakis et al. , 2018) . Disruption of the ECM and intercellular adhesion are important steps in cancer cell motility and metastasis (Xia et al. , 2015) .  \nECM degradation is involved in the transition from an epithelial cell phenotype to a mesenchymal cell phenotype, a process known as the epithelial-mesenchymal transition (EMT)(Agraval and Yadav, 2019) . Proteoglycans, glycoproteins, matrix metalloproteinases (MMPs), and growth factors regulate ECM function (Guan et al. , 2018; Kessenbrock et al. , 2010; Tzanakakis et al","cbCairlq20a1c9I9","https://ap.wps.com/l/cbCairlq20a1c9I9","pdf",9893152,13,"English","# Abstract\n# Introduction\n## Tumor microenvironment and metastasis\n## Extracellular matrix disruption and MMP9\n## Epithelial-mesenchymal transition (EMT)","[{\"question\":\"What therapeutic challenge does the study address?\",\"answer\":\"Distant metastasis and acquired resistance reduce the effectiveness of chemotherapy and molecularly targeted therapies.\"},{\"question\":\"Which molecular target do the monoterpene indole alkaloids aim to affect?\",\"answer\":\"They target matrix metalloproteinase 9 (MMP9), which is linked to extracellular matrix degradation and cancer-cell motility.\"},{\"question\":\"How were the antimetastatic effects evaluated?\",\"answer\":\"The study used assays for cell viability, migration, and invasion, along with qRT-PCR, pathway-focused expression analysis, Western blotting, reporter assays, molecular docking, and target prediction.\"}]","Unveiling the antimetastatic activity of monoterpene indole alkaloids targeting MMP9 in cancer cells | PDF",1789999748,33]