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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

New findings on the antiproliferative activity of the silver(I) complex with 5-fluorouracil against human multi-resistant NCI/ADR-RES ovarian tumor cells

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Bormio Nunes, Julia H. [1, 2] ; de Paiva, Paula P. [1, 3] ; Ruiz, Ana Lucia T. G. [1, 3] ; de Carvalho, Joao Ernesto [3] ; Corbi, Pedro P. [2]
Total Authors: 5
[1] Univ Campinas UNICAMP, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, BR-13148218 Paulinia, SP - Brazil
[2] Univ Campinas UNICAMP, Inorgan Chem Dept, BR-13083970 Campinas, SP - Brazil
[3] Univ Gamines UNICAMP, Fac Pharmaceut Sci, BR-13081970 Campinas, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: TOXICOLOGY IN VITRO; v. 60, p. 359-368, OCT 2019.
Web of Science Citations: 1

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. (AU)

FAPESP's process: 18/12062-4 - Synthesis, characterization and studies of interaction with biomolecules of metal complexes containing biologically active ligands: a strategy in the preparation of new agents with antibacterial and antiviral activities
Grantee:Pedro Paulo Corbi
Support type: Regular Research Grants
FAPESP's process: 15/25114-4 - Synthesis of New Ag(I), Cu(II), Pd(II) and Pt(II) complexes based on sulfonamides and derivatives: antibacterial activities and application prospects on skin critically colonized wounds
Grantee:Pedro Paulo Corbi
Support type: Regular Research Grants