Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions.
J Leukoc Biol
; 76(1): 169-75, 2004 Jul.
Article
em En
| MEDLINE
| ID: mdl-15075348
ABSTRACT
The protein complex S100A8/A9, abundant in the cytosol of neutrophils, is secreted from the cells upon cellular activation and induces apoptosis in tumor cell lines and normal fibroblasts in a zinc-reversible manner. In the present study, we present evidence that the S100A8/A9 also exerts its apoptotic effect by a zinc-independent mechanism. Treatment of the colon carcinoma cells with different concentrations of human S100A8/A9 or the metal ion chelator diethylenetriaminepentacetic acid (DTPA) resulted in a significant increase of cell death. Annexin V/phosphatidylinositol and Hoechst 33258 staining revealed that cell death was mainly of the apoptotic type. A significant increase in the activity of caspase-3 and -9 was observed in both cell lines after treatment. Caspase-8 activation was negligible in both cell lines. The cytotoxicity/apoptotic effect of human S100A8/A9 and DTPA was inhibited significantly (P<0.05) by Zn(+2) and Cu(+2), more effectively than by Ca(2+) and Mg(2+). The antioxidant N-acetyl-L-cysteine inhibited the cytotoxicity/apoptotic effect of S100A8/A9 and DTPA. However, as a result of the different time-courses of both agents and that the S100A8/A9-induced apoptosis was not completely reversed, we conclude that S100A8/A9 exerts its apoptotic effect on two colon carcinoma cell lines through a dual mechanism one via zinc exclusion from the target cells and the other through a yet-undefined mechanism, probably relaying on the cell-surface receptor(s).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
/
Apoptose
/
Neoplasias do Colo
/
Calgranulina A
/
Calgranulina B
/
Metais
Limite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Irã