The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells
Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC<...
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2025-01-01
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| author | Libor Sokoli Peter Takáč Mariana Budovská Radka Michalková Martin Kello Natália Nosálová Ľudmila Balážová Šimon Salanci Ján Mojžiš |
| author_facet | Libor Sokoli Peter Takáč Mariana Budovská Radka Michalková Martin Kello Natália Nosálová Ľudmila Balážová Šimon Salanci Ján Mojžiš |
| author_sort | Libor Sokoli |
| collection | DOAJ |
| description | Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC<sub>50</sub> values of 5.8 ± 0.3 μmol/L for HCT116 cells and 6.1 ± 2.1 μmol/L for Caco2 cells. Flow cytometry and Western blot analysis were employed to investigate the molecular mechanisms underlying cytotoxicity, proapoptotic action, and anti-invasion effects. The proapoptotic activity was evidenced by the activation of caspases 3 and 7, mitochondrial dysfunction, and an increased number of apoptotic cells, confirmed by annexin V/PI and AO/PI staining. Additionally, MB-653 induces dose-dependent G2/M phase cell cycle arrest, the cause of which could be cyclin B1/CDC2 complex dysfunction and/or a decrease in α-tubulin protein expression. Another important observation was that MB-653 modulated several signalling pathways associated with various cellular activities, including survival, proliferation, tumour invasiveness, metastasis, and epithelial–mesenchymal transition (EMT). We further demonstrated its safety for topical and parenteral application. To sum up, our results indicate the real potential of MB-653 in treating colorectal cancer. |
| format | Article |
| id | doaj-art-f553a2c806974e9cb7c2f36bc8967ae0 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-f553a2c806974e9cb7c2f36bc8967ae02025-01-24T13:25:04ZengMDPI AGBiomolecules2218-273X2025-01-011517210.3390/biom15010072The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer CellsLibor Sokoli0Peter Takáč1Mariana Budovská2Radka Michalková3Martin Kello4Natália Nosálová5Ľudmila Balážová6Šimon Salanci7Ján Mojžiš8Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, SlovakiaDepartment of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, SlovakiaDepartment of Organic Chemistry, Institute of Chemistry, Faculty of Science, Pavol Jozef Šafárik University, 040 01 Košice, SlovakiaDepartment of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, SlovakiaDepartment of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, SlovakiaSmall Animal Clinic, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, SlovakiaDepartment of Pharmaceutical Technology, Pharmacognosy and Botany, University of Veterinary Medicine and Pharmacy, 041 81 Košice, SlovakiaDepartment of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, SlovakiaDepartment of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, SlovakiaColorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC<sub>50</sub> values of 5.8 ± 0.3 μmol/L for HCT116 cells and 6.1 ± 2.1 μmol/L for Caco2 cells. Flow cytometry and Western blot analysis were employed to investigate the molecular mechanisms underlying cytotoxicity, proapoptotic action, and anti-invasion effects. The proapoptotic activity was evidenced by the activation of caspases 3 and 7, mitochondrial dysfunction, and an increased number of apoptotic cells, confirmed by annexin V/PI and AO/PI staining. Additionally, MB-653 induces dose-dependent G2/M phase cell cycle arrest, the cause of which could be cyclin B1/CDC2 complex dysfunction and/or a decrease in α-tubulin protein expression. Another important observation was that MB-653 modulated several signalling pathways associated with various cellular activities, including survival, proliferation, tumour invasiveness, metastasis, and epithelial–mesenchymal transition (EMT). We further demonstrated its safety for topical and parenteral application. To sum up, our results indicate the real potential of MB-653 in treating colorectal cancer.https://www.mdpi.com/2218-273X/15/1/72indole phytoalexinscolorectal cancerapoptosismetastasisEMT |
| spellingShingle | Libor Sokoli Peter Takáč Mariana Budovská Radka Michalková Martin Kello Natália Nosálová Ľudmila Balážová Šimon Salanci Ján Mojžiš The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells Biomolecules indole phytoalexins colorectal cancer apoptosis metastasis EMT |
| title | The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells |
| title_full | The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells |
| title_fullStr | The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells |
| title_full_unstemmed | The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells |
| title_short | The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells |
| title_sort | proapoptotic effect of mb 653 is associated with the modulation of metastasis and invasiveness related signalling pathways in human colorectal cancer cells |
| topic | indole phytoalexins colorectal cancer apoptosis metastasis EMT |
| url | https://www.mdpi.com/2218-273X/15/1/72 |
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