N-acetylcysteine blocks apoptosis induced by N-alpha-tosyl-L-phenylalaninechloromethyl ketone in transformed T-cells

The serine protease inhibitor N-alpha-tosyl-L-phenylalanine chloromethyl ke tone (TPCK) can interfere with cell-cycle progression and has also been sho wn either to protect cells from apoptosis or to induce apoptosis, We tested the effect of TPCK on two transformed T-cell lines. Both Jurkat T-cells an d Theileria parva-transformed T-cells were shown to be highly sensitive to TPCK-induced growth arrest and apoptosis. Surprisingly, we found that the t hiol antioxidant, N-acetylcysteine (NAC), as well as L- or D-cysteine block ed TPCK induced growth arrest and apoptosis. TPCK inhibited constitutive NF -kappa B activation in T. parva-transformed T-cells, with phosphorylation o f I kappa B alpha and I kappa B beta being inhibited with different kinetic s; TPCK-mediated inhibition of I kappa B phosphorylation, NF-kappa B DNA bi nding and transcriptional activity were also prevented by NAC or cysteine, Our observations indicate that apoptosis and NF-kappa B inhibition induced by TPCK result from modifications of sulphydryl groups on proteins involved in regulating cell survival and the NF-kappa B activation pathway(s).