Stimulation of Fas agonistic antibody–mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity

Abstract

We report that in Jurkat T cells or freshly isolated T lymphocytes, physiological concentrations of highmolecular weight sulfated polysaccharides such as heparin, heparan sulfate, and dextran sulfate significantly increased the percentage of cell death induced by Fas IgM agonistic antibody. The phenomenon was caspase dependent and P53 independent and correlated with an increased accessibility of cell surface Fas receptors. We also observed that the Fas IgM agonistic antibody-dependent formation of sodium dodecyl sulfate (SDS)-resistant large structures containing Fas receptor was decreased in the presence of heparin-like agents. In contrast, the different agents had no effect when cell death was triggered by FasL, the natural ligand of Fas that does not generate SDS-resistant forms of Fas. Interestingly, the synergistic effect of heparin-like agents toward Fas IgM agonistic antibody-mediated cell death abolished Hsp27 antiapoptotic activity but did not alter much the protection generated by Bcl-2 expression.

Caspases activation in hyperthermia-induced stimulation of TRAIL apoptosis

“…Heat treatment was performed at 42±0.1°C in a thermostatic Huber water bath (Fisher Bioblock Scientific, Illkirch, France). Jurkat human T-lymphocytes line has already been described (Manero et al 2004;Moulin et al 2007a). Cells were grown at 37°C in the presence of 5% CO 2 in Roswell Park Memorial Institute medium supplemented with 10% fetal calf serum and 50 U/ml penicillin/streptomycin (Invitrogen, Cergy Pontoise, France).…”

Polyanionic Drugs and Viral Oncogenesis: a Novel Approach to Control Infection, Tumor-associated Inflammation and Angiogenesis

“…different natural PS compounds exert an anti-tumor activity acting directly on tumor cells. Heparin, HS, dextran sulfate and fucoidan induce apoptosis of hepatoma and lymphoma cells [ 137 , 138 ]. Various PS polysaccharides inhibit tumour metastasis by blocking tumour-derived glycosidases and proteases such as heparanases [ 139 ] and matrix metallo proteinases [ 140 ].…”