Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions

Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines : the role of ROS and the effect of metal ions

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).

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
NATURVETENSKAP Biologi Cellbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Cell Biology hsv//eng
NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
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

Kerkhoff, C.Institute of Experimental Dermatology, Münster, Germany (författare)
Los, Marek JanInstitute of Experimental Dermatology, Münster, Germany(Swepub:liu)marlo14 (författare)
Hashemi, M.Tarbiat Modarres University, Tehran, Iran (författare)
Sorg, C.Institute of Experimental Dermatology, Münster, Germany (författare)
Karami-Tehrani, F.Tarbiat Modarres University, Tehran, Iran (författare)
Tarbiat Modarres University, Tehran, IranInstitute of Experimental Dermatology, Münster, Germany (creator_code:org_t)

Ingår i:Journal of Leukocyte Biology: Oxford University Press (OUP)76:1, s. 169-1750741-54001938-3673

Av författaren/redakt...: Ghavami, Saeid; Kerkhoff, C.; Los, Marek Jan; Hashemi, M.; Sorg, C.; Karami-Tehrani, ...

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