5th World Congress on Cancer Therapy
Ludwig Boltzmann Institute for Rheumatology, Austria
Title: A persulfide analog of the nitrosothiol SNAP, D-P*, induces apoptotic cell death in Jurkat leukemia T-cells
Biography: Burkhard Kloesch
Background/Aim: Many studies have reported about the controversial role of hydrogen sulfi de (H2S) in cell survival, proliferation and apoptosis. In the present work, two H2S-releasing compounds, sodium hydrogen sulfi de (NaHS) and D-P*, a novel persulfi de analog of the nitrosothiol S-nitroso-N-acetyl-D,L-penicillamine, were selected for evaluation of their antiproliferative and pro-apoptotic potential in Jurkat leukemia T-cells. Materials and Methods: Jurkat leukemia T-cells were stimulated with phorbol 12-myristate 13- acetate and the calcium ionophore A23187 in the absence or presence of diff erent concentrations of NaHS or D-P* (0.125 – 1 mM). Interleukin-2 (IL- 2) production was analyzed by enzyme-linked immunosorbent assay. Proliferation and cell viability were monitored by 2,3-bis- (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, annexin-V/7-amino-actinomycin D staining and western blot. Results: Both H2S donors eff ectively blocked IL-2 synthesis in Jurkat T-cells. In contrast to NaHS, D-P* dramatically reduced proliferation and cell viability of Jurkat T-cells. D-P* induced cleavage of caspase-3/-7, poly (ADP-ribose) polymerase, myeloid cell leukemia-1 and β-catenin. High concentrations of the anti-oxidant N-acetyl-cysteine could completely block programmed cell death. Conclusion: In contrast to the “classic” H2S donor NaHS, the novel and slow-releasing H2S donor D-P* showed potent antiproliferative and pro-apoptotic activities in Jurkat leukemia T-cells suggesting that D-P* led to an imbalance in the redox system (GSH depletion?) which in turn induced apoptosis.