Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis
Mebendazole (MBZ), a benzimidazole anthelmintic and cytoskeleton-disrupting compound, exhibits antitumor properties; however, its action on ovarian cancer (OC) is not clearly understood. This study evaluates the effect of MBZ on OC cell lines OVCAR3 and OAW42, focusing on cell proliferation, migrati...
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2025-01-01
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| author | Rahul Gupta Dipanjan Roy Arijit Ghosh Yasmin Begum Dipanjan Ghosh Snehasikta Swarnakar |
| author_facet | Rahul Gupta Dipanjan Roy Arijit Ghosh Yasmin Begum Dipanjan Ghosh Snehasikta Swarnakar |
| author_sort | Rahul Gupta |
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| description | Mebendazole (MBZ), a benzimidazole anthelmintic and cytoskeleton-disrupting compound, exhibits antitumor properties; however, its action on ovarian cancer (OC) is not clearly understood. This study evaluates the effect of MBZ on OC cell lines OVCAR3 and OAW42, focusing on cell proliferation, migration, invasion, and cancer stemness. The underlying mechanisms, including cytoskeletal disruption, epithelial–mesenchymal transition (EMT), and signaling pathways, were explored. MBZ inhibited OVCAR3 and OAW42 cell proliferation in a dose- and time-dependent manner. Additionally, MBZ significantly impedes migration, spheroid invasion, colony formation, and stemness. In addition, it reduced actin polymerization and down-regulated CSC markers (e.g., CD24, CD44, EpCAM). Moreover, MBZ suppressed MMP-9 activity and inhibited the EMT marker as judged by decreased N-Cadherin and Vimentin and increased E-Cadherin. Furthermore, MBZ induced G2/M cell cycle arrest by modulating Cyclin B1, CDC25C, and WEE1. Also, it triggered apoptosis by disrupting mitochondrial membrane potential. Mechanistic studies revealed a significant downregulation of Girdin, an Akt modulator, along with reduced p-Akt, p-IKKα/β, and p-NF-κB, indicating MBZ’s novel mechanism of action through the Girdin-mediated Akt/IKKα/β/NF-κB signaling axis. Thus, by targeting Girdin, MBZ presents a promising repurposed therapeutic strategy to inhibit cancer cell proliferation and metastasis in ovarian cancer. |
| format | Article |
| id | doaj-art-3da1bb61d40748adb97b9f0821563244 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Cells |
| spelling | doaj-art-3da1bb61d40748adb97b9f08215632442025-01-24T13:26:43ZengMDPI AGCells2073-44092025-01-0114211310.3390/cells14020113Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling AxisRahul Gupta0Dipanjan Roy1Arijit Ghosh2Yasmin Begum3Dipanjan Ghosh4Snehasikta Swarnakar5Infectious Diseases & Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, IndiaDepartment of Natural Products, National Institute of Pharmaceutical Education and Research, Kolkata 700054, IndiaDepartment of Molecular Biology, Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata 700094, IndiaInfectious Diseases & Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, IndiaDepartment of Natural Products, National Institute of Pharmaceutical Education and Research, Kolkata 700054, IndiaInfectious Diseases & Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, IndiaMebendazole (MBZ), a benzimidazole anthelmintic and cytoskeleton-disrupting compound, exhibits antitumor properties; however, its action on ovarian cancer (OC) is not clearly understood. This study evaluates the effect of MBZ on OC cell lines OVCAR3 and OAW42, focusing on cell proliferation, migration, invasion, and cancer stemness. The underlying mechanisms, including cytoskeletal disruption, epithelial–mesenchymal transition (EMT), and signaling pathways, were explored. MBZ inhibited OVCAR3 and OAW42 cell proliferation in a dose- and time-dependent manner. Additionally, MBZ significantly impedes migration, spheroid invasion, colony formation, and stemness. In addition, it reduced actin polymerization and down-regulated CSC markers (e.g., CD24, CD44, EpCAM). Moreover, MBZ suppressed MMP-9 activity and inhibited the EMT marker as judged by decreased N-Cadherin and Vimentin and increased E-Cadherin. Furthermore, MBZ induced G2/M cell cycle arrest by modulating Cyclin B1, CDC25C, and WEE1. Also, it triggered apoptosis by disrupting mitochondrial membrane potential. Mechanistic studies revealed a significant downregulation of Girdin, an Akt modulator, along with reduced p-Akt, p-IKKα/β, and p-NF-κB, indicating MBZ’s novel mechanism of action through the Girdin-mediated Akt/IKKα/β/NF-κB signaling axis. Thus, by targeting Girdin, MBZ presents a promising repurposed therapeutic strategy to inhibit cancer cell proliferation and metastasis in ovarian cancer.https://www.mdpi.com/2073-4409/14/2/113mebendazolegirdinMMP-9EMTovarian cancermetastasis |
| spellingShingle | Rahul Gupta Dipanjan Roy Arijit Ghosh Yasmin Begum Dipanjan Ghosh Snehasikta Swarnakar Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis Cells mebendazole girdin MMP-9 EMT ovarian cancer metastasis |
| title | Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis |
| title_full | Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis |
| title_fullStr | Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis |
| title_full_unstemmed | Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis |
| title_short | Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis |
| title_sort | mebendazole exerts anticancer activity in ovarian cancer cell lines via novel girdin mediated akt ikkα β nf κb signaling axis |
| topic | mebendazole girdin MMP-9 EMT ovarian cancer metastasis |
| url | https://www.mdpi.com/2073-4409/14/2/113 |
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