Characterization of the anti-Leishmania effect induced by cisplatin, an anticancer drug

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

Tavares, J (Autor) FFUP; Ouaissi, M (Autor) Outra; Ouaissi, A (Autor) Outra; Cordeiro da Silva, A (Autor) FFUP

Revista

Título: Acta Tropica

Vol. 103 Nº 2

Páginas: 133-141

ISSN: 0001-706X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 23 Citações

Scopus - 26 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Ciências da saúde

Outras Informações

ID Authenticus: P-004-88H

DOI: 10.1016/j.actatropica.2007.05.017

Abstract (EN): The cis-diamminedichloroplatinum(II), known as cis-DDP or cisplatin is a widely used drug in cancer chemotherapy. Although a recent study has shown the anti-Leishmania activity of some cis-DDP derivatives, the cytotoxic properties were measured only on promastigotes, the insect vector form of the parasite. In this study the effect of cis-DDP on promastigotes and amastigotes, the vertebrate stage of the parasite is reported. The IC50, determined by flow cytometry, after 72 It of drug incubation was four times higher, 7.73 +/- 1.03 mu M in the case of promastigotes compared to axenic amastigotes, 1.88 +/- 0.10 mu M. In intracellular amastigotes the IC50, determined by counting the parasite index was 1.85 +/- 0.22 mu M. By using flow cytometry, two patterns of cell cycle changes was observed: cis-DDP treated promastigotes and amastigotes accumulated in S phase and G2 phase, respectively. The cis-DDP response was also found to involve an "apoptosis-like" death of both promastigotes and amastigotes. However, DNA fragmentation was only detected in promastigote forms. In contrast mitochondrial transmembrane potential loss was observed for both stages of the parasite. Upon incubation of parasites with the drug an increase on GSH and GSSG levels and reactive oxygen species could be detected in the case of promastigote. Moreover, a slight increase of GSH level was detected on amastigote form. Taken together, these observations indicate that amastigotes are more sensitive to cis-DDP when compared to promastigotes. However, the signaling pathways leading to cell death could be different.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9