| Full text | |
| Author(s): |
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
|
| Affiliation: | [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 |
| Abstract | |
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 Opportunities: | 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 Opportunities: | Regular Research Grants |