An ICE‐like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytic THP.1 cells

Inhibition of caspase proteases by CrmA enhances the resistance of human leukemic cells to multiple chemotherapeutic agents

“…By achieving constitutive cells, 36 and Z-VAD-FMK inhibits the rate of cell death in VP-16-treated THP.1 cells. 37 Our results using CrmA-expressing downmodulation of caspase activities in Jurkat cells through expression of CrmA, we have been able to study the longcells are consistent with these findings, and demonstrate that inhibition of CrmA-sensitive caspases confers enhanced celluterm recovery of cells transiently exposed to drugs. Our findings show that CrmA-expressing cells eventually recovered lar resistance to multiple different chemotherapy drugs.…”

“…[6][7][8] Although these hallmark VP-16-treated HL-60 cells, 36 and benzyloxycarbonyl-VADfeatures are commonly observed in drug-induced apoptosis, fluoromethyl ketone (Z-VAD-FMK) inhibits the rate of cell relatively little is known about the signaling pathways which death in VP-16-treated THP.1 human monocytic cells. 37 are initiated in response to cellular damage. The components Studies using peptide inhibitors have examined the kinetics of these unknown pathways represent potential targets for of drug-induced apoptosis over only relatively short time novel therapies.…”

“…In our experiments, tor of caspase-1 (ICE), but a less potent inhibitor of caspase-3 (CPP32) and caspase-2 (ICH-1). 19,25,32,37 Perhaps the reduced Discussion ability of CrmA, relative to Bcl-2, to inhibit DOX-and VP-16-induced cell death is a reflection of the specific caspases The molecular signaling pathways which are initiated in activated by these drugs. Alternatively, Bcl-2 may have other response to chemotherapy-induced cellular damage, and lead anti-apoptotic activities which are independent of caspase to the eventual apoptotic death of the cell, are largely undeproteases.…”

An interleukin‐1β‐converting enzyme‐like protease is a common mediator of apoptosis in thymocytes

“…Recently Z-VAD.FMK has also been shown to inhibit Fasinduced apoptosis in Jurkat cells and apoptosis induced by diverse stimuli in the human monocytic tumour cell line, 40]. The high concentrations of Z-VAD.FMK required for inhibition of apoptosis in thymocytes may have been due to poor cellular permeability compared to Jurkat or THP-1 cells or to nonspecific effects.…”

“…Fluoromethyl ketones are, however, much less reactive than the corresponding chloromethyl ketones [41] and so their lack of toxicity at high concentrations (Table 1) suggested they were not reacting nonspecifically. Alternatively high concentrations of Z-VAD.FMK may have been required to inhibit a homologue(s) of ICE different from those found in Jurkat and THP-1 cells [39,40]. Specific inhibitors of ICE have an aspartate in the P, position together with four amino acid residues to the left of the cleavage site [3 11.…”