Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells
AbstractColon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertaken so far, including the use of drug cocktails and polypharmacology. Heme oxygenase-1 (HO-1) is...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2337191 |
| _version_ | 1797201667791257600 |
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| author | Loredana Salerno Antonietta Notaro Valeria Consoli Federica Affranchi Valeria Pittalà Valeria Sorrenti Luca Vanella Michela Giuliano Sebastiano Intagliata |
| author_facet | Loredana Salerno Antonietta Notaro Valeria Consoli Federica Affranchi Valeria Pittalà Valeria Sorrenti Luca Vanella Michela Giuliano Sebastiano Intagliata |
| author_sort | Loredana Salerno |
| collection | DOAJ |
| description | AbstractColon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertaken so far, including the use of drug cocktails and polypharmacology. Heme oxygenase-1 (HO-1) is an emerging molecular target in the treatment of various cancers. We recently demonstrated that a combination of HO-1 inhibitors with 5-FU and the corresponding hybrids SI1/17, SI1/20, and SI1/22, possessed anticancer activity against prostate and lung cancer cells. In this work, we evaluated these hybrids in a model of colon cancer and found that SI1/22 and the respective combo have greater potency than 5-FU. Particularly, compounds inhibit HO-1 activity in cell lysates, increase ROS and the expression of HO-1, SOD, and Nrf2. Moreover, we observed a decrease of pro-caspase and an increase in cleaved PARP-1 and p62, suggesting apoptotic and autophagic cell death and potential application of these drugs as anticancer agents. |
| first_indexed | 2024-04-24T07:51:11Z |
| format | Article |
| id | doaj.art-7cbdfd4d092d43a08cfd45bb07e543c4 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-24T07:51:11Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7cbdfd4d092d43a08cfd45bb07e543c42024-04-18T12:17:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2337191Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cellsLoredana Salerno0Antonietta Notaro1Valeria Consoli2Federica Affranchi3Valeria Pittalà4Valeria Sorrenti5Luca Vanella6Michela Giuliano7Sebastiano Intagliata8Department of Drug and Health Sciences, University of Catania, Catania, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, ItalyDepartment of Drug and Health Sciences, University of Catania, Catania, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, ItalyDepartment of Drug and Health Sciences, University of Catania, Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, Catania, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, ItalyDepartment of Drug and Health Sciences, University of Catania, Catania, ItalyAbstractColon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertaken so far, including the use of drug cocktails and polypharmacology. Heme oxygenase-1 (HO-1) is an emerging molecular target in the treatment of various cancers. We recently demonstrated that a combination of HO-1 inhibitors with 5-FU and the corresponding hybrids SI1/17, SI1/20, and SI1/22, possessed anticancer activity against prostate and lung cancer cells. In this work, we evaluated these hybrids in a model of colon cancer and found that SI1/22 and the respective combo have greater potency than 5-FU. Particularly, compounds inhibit HO-1 activity in cell lysates, increase ROS and the expression of HO-1, SOD, and Nrf2. Moreover, we observed a decrease of pro-caspase and an increase in cleaved PARP-1 and p62, suggesting apoptotic and autophagic cell death and potential application of these drugs as anticancer agents.https://www.tandfonline.com/doi/10.1080/14756366.2024.2337191Hybridsmutual prodrugs5-fluorouracilheme oxygenase 1HTC116 colorectal cancer cells |
| spellingShingle | Loredana Salerno Antonietta Notaro Valeria Consoli Federica Affranchi Valeria Pittalà Valeria Sorrenti Luca Vanella Michela Giuliano Sebastiano Intagliata Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells Journal of Enzyme Inhibition and Medicinal Chemistry Hybrids mutual prodrugs 5-fluorouracil heme oxygenase 1 HTC116 colorectal cancer cells |
| title | Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells |
| title_full | Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells |
| title_fullStr | Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells |
| title_full_unstemmed | Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells |
| title_short | Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells |
| title_sort | evaluation of the anticancer effects exerted by 5 fluorouracil and heme oxygenase 1 inhibitor hybrids in htc116 colorectal cancer cells |
| topic | Hybrids mutual prodrugs 5-fluorouracil heme oxygenase 1 HTC116 colorectal cancer cells |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2337191 |
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