The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells
Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the c...
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MDPI AG
2021-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/7/2045 |
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| author | Agnieszka Gornowicz Anna Szymanowska Mariusz Mojzych Robert Czarnomysy Krzysztof Bielawski Anna Bielawska |
| author_facet | Agnieszka Gornowicz Anna Szymanowska Mariusz Mojzych Robert Czarnomysy Krzysztof Bielawski Anna Bielawska |
| author_sort | Agnieszka Gornowicz |
| collection | DOAJ |
| description | Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim. |
| first_indexed | 2024-03-10T12:38:55Z |
| format | Article |
| id | doaj.art-aeda0207cb0a429f9c280cf280a590e6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:38:55Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-aeda0207cb0a429f9c280cf280a590e62023-11-21T14:05:33ZengMDPI AGMolecules1420-30492021-04-01267204510.3390/molecules26072045The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer CellsAgnieszka Gornowicz0Anna Szymanowska1Mariusz Mojzych2Robert Czarnomysy3Krzysztof Bielawski4Anna Bielawska5Department of Biotechnology, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Biotechnology, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Chemistry, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, PolandDepartment of Synthesis and Technology of Drugs, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Synthesis and Technology of Drugs, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Biotechnology, Medical University of Bialystok, 15-222 Bialystok, PolandCancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim.https://www.mdpi.com/1420-3049/26/7/2045colorectal cancerapoptosiscell signalinganticancer agentspyrazolo[4,3-<i>e</i>]tetrazolo[1,5-<i>b</i>][1,2,4]triazine5-fluorouracil |
| spellingShingle | Agnieszka Gornowicz Anna Szymanowska Mariusz Mojzych Robert Czarnomysy Krzysztof Bielawski Anna Bielawska The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells Molecules colorectal cancer apoptosis cell signaling anticancer agents pyrazolo[4,3-<i>e</i>]tetrazolo[1,5-<i>b</i>][1,2,4]triazine 5-fluorouracil |
| title | The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells |
| title_full | The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells |
| title_fullStr | The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells |
| title_full_unstemmed | The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells |
| title_short | The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells |
| title_sort | anticancer action of a novel 1 2 4 triazine sulfonamide derivative in colon cancer cells |
| topic | colorectal cancer apoptosis cell signaling anticancer agents pyrazolo[4,3-<i>e</i>]tetrazolo[1,5-<i>b</i>][1,2,4]triazine 5-fluorouracil |
| url | https://www.mdpi.com/1420-3049/26/7/2045 |
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