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(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGY IN VITRO; v. 60, p. 359-368, OCT 2019.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 18/12062-4 - Síntese, caracterização e estudos de interação com biomoléculas de complexos metálicos contendo ligantes biologicamente ativos: uma estratégia na preparação de novos agentes com atividades antibacterianas e antivirais
• Beneficiário: Pedro Paulo Corbi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/25114-4 - Preparação de novos complexos de Ag(I), Cu(II), Pd(II) e Pt(II) à base de sulfonamidas e derivados: estudos de atividade antibacteriana e perspectivas de aplicação em lesões de pele criticamente colonizadas.
• Beneficiário: Pedro Paulo Corbi
• Modalidade de apoio: Auxílio à Pesquisa - Regular