Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Background & Aim: Numerous studies have reported about the different role of H2S in cell survival, proliferation and apoptosis in human cancer cell lines. In the present work, we investigated the anti-proliferative and pro-apoptotic potential of substance P* in Jurkat leukemia T cells. P* is a persulfide analog of the nitrosothiol S-nitroso-N-acetyl-D,L-penicillamine (SNAP) which releases H2S only in the presence of thiols (reduced glutathione or L-cysteine). Materials & Methods: Proliferation and cell viability of Jurkat T cells were determined with 2,3-bis-(2-methoxy-4-nitro-5- sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, Annexin-V/7-AAD staining and Western blot. To induce cytokine production, the cells were stimulated with phorbol 12-myristate 13-acetate plus A23187 with or without different concentrations of P*. The release of interleukin (IL-) 2 was quantified by enzyme-linked immunosorbent assay. Results: Substance P* reduced proliferation and cell viability of Jurkat T cells in a dose-dependent manner. P* induced cleavage of pro-caspase-3/-7, poly (ADP-ribose) polymerase, myeloid cell leukemia-1 and β-catenin. The addition of high concentrations of antioxidants such as N-acetyl-cysteine or L-cysteine could completely prevent apoptotic cell death of Jurkat T cells. In strong contrast to P*, the “classic” H2S donor sodium hydrogen sulfide (NaHS) did not affect cell viability. Besides the pro-apoptotic activities of P*, it also blocked IL-2 synthesis. Conclusion: The slow-releasing and thiol-inducible H2S donor P* showed potent antiproliferative and pro-apoptotic activities in Jurkat leukemia T cells. We suggest that treatment of Jurkat T cells with P* may lead to an imbalance in the redox system (GSH depletion?) which in turn induces the apoptotic (caspase-3) signaling pathway.

Biography

Email: burkhard.kloesch@gmx.at