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

• Type: Article in International Scientific Journal
• Date: 2007

Authors

J. Tavares (Author) Other; A. Ouaissi (Author) Other; M. Ouaissi (Author) Other; A. Cordeiro-da-Silva (Author) FFUP

Journal

Title: Acta Tropica

Vol. 103 No. 2

Pages: 133-141

ISSN: 0001-706X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 23 Citations

ISI Web of Science

Scopus - 26 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

CORDIS: Health sciences

Other information

Authenticus ID: P-004-88H

Resumo (PT): 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 h of drug incubation was four times higher, 7.73±1.03M in the case of promastigotes compared to axenic amastigotes, 1.88±0.10M. In intracellular amastigotes the IC50, determined by counting the parasite index was 1.85±0.22M. 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. <br> <br> Keywords: Cisplatin; Leishmania infantum; Anticancer drug; Cell death <br> <a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1R-4NWCH05-1&_user=2460038&_coverDate=08%2F31%2F2007&_rdoc=8&_fmt=high&_orig=browse&_srch=doc-info(%23toc%234897%232007%23998969997%23666399%23FLA%23display%23Volume)&_cdi=4897&_sort=d&_docanchor=&_ct=10&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=5b10df0cad60d56252382f65ceceeb99"> Texto integral </a> <br> <br>

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 h of drug incubation was four times higher, 7.73±1.03M in the case of promastigotes compared to axenic amastigotes, 1.88±0.10M. In intracellular amastigotes the IC50, determined by counting the parasite index was 1.85±0.22M. 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. <br> <br> Keywords: Cisplatin; Leishmania infantum; Anticancer drug; Cell death <br> <a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1R-4NWCH05-1&_user=2460038&_coverDate=08%2F31%2F2007&_rdoc=8&_fmt=high&_orig=browse&_srch=doc-info(%23toc%234897%232007%23998969997%23666399%23FLA%23display%23Volume)&_cdi=4897&_sort=d&_docanchor=&_ct=10&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=5b10df0cad60d56252382f65ceceeb99"> Full text </a> <br> <br>

Language: Portuguese

Type (Professor's evaluation): Scientific