Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions
2004 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 76, no 1, 169-175 p.Article in journal (Refereed) Published
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 SI00A8/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 SI00A8/A9 and DTPA was inhibited significantly 2 2 (P<0.05) by Zn+2 and Cu+2, more effectively than by Ca2+ and Mg2+. The antioxidant N-acetyl-L-cysteine inhibited the cytotoxicity/apoptotic effect of SI00A8/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).
Place, publisher, year, edition, pages
2004. Vol. 76, no 1, 169-175 p.
Antimicrobial activity, arachidonic-acid, calcium-binding protein, calprotectin, caspase activation, cytotoxic peptides, endothelial-cells, human neutrophils, inhibitory-factor, peritoneal-exudate cells, polymorphonuclear neutrophils, s100 protein, zinc-binding, zinc-binding protein
Cancer and Oncology Cell Biology Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-87002DOI: 10.1189/jlb.0903435ISI: 000222283400021OAI: oai:DiVA.org:liu-87002DiVA: diva2:584203