New findings on the antiproliferative activity of the silver(I) complex with 5-fluorouracil against human multi-resistant NCI/ADR-RES ovarian tumor cells
| Autor: | Pedro P. Corbi, Paula Pereira de Paiva, Julia Helena Bormio Nunes, João Carvalho, Ana Lúcia Tasca Gois Ruiz |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Silver Antineoplastic Agents Apoptosis Phosphatidylserines Toxicology NCI/ADR-RES Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Humans Cell Proliferation Cisplatin chemistry.chemical_classification Membrane Potential Mitochondrial Ovarian Neoplasms Reactive oxygen species medicine.diagnostic_test Intrinsic apoptosis General Medicine Phosphatidylserine Cell cycle In vitro Drug Resistance Multiple 030104 developmental biology chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Female Fluorouracil medicine.drug |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 60 |
| ISSN: | 1879-3177 |
| Popis: | Metal complexes with antitumor activities have been studied as an alternative to overcome tumor resistance to current pharmaceuticals. Recently, we described the synthesis of a silver(I) complex with 5-fluorouracil (Ag-5fu) with an effective activity in vitro against human multi-resistant ovarian tumor cells (NCI/ADR-RES) when compared to 5-fluorouracil (5fu) and cisplatin. Therefore, for a better understanding of the effect of Ag-5fu and its precursors 5fu and silver(I), the compounds were evaluated by colony formation capacity and flow cytometry assays to analyze cell cycle and cell death induction [phosphatidylserine residues (PS) exposition, multicaspases activation, production of reactive oxygen species (ROS) and mitochondrial membrane depolarization] on NCI/ADR-RES tumor cells. As observed for 5fu, Ag-5fu was able to promote G1 phase arrest and to totally inhibit colony formation. Besides, as observed to AgNO3, Ag-5fu promoted a potent PS externalization and multicaspases activation with loss of plasmatic membrane integrity. None of the compounds induced reactive oxygen species (ROS) generation. The Ag-5fu promoted mitochondrial membrane depolarization over time. The results suggest that Ag-5fu may induce regulated cell death in NCI/ADR-RES cells probably by intrinsic apoptosis. Silver(I) and 5fu play different roles on the effect of Ag-5fu in NCI/ADR-RES cells, and the activity of the Ag-5fu complex seems to be more than a simple combination of the activities of free 5fu and silver(I) ions. |
| Databáze: | OpenAIRE |
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