We report for the first time a potent apoptotic effect of omeprazole (OM). Apoptosis was induced in Jurkat cells in a time and concentration-dependent mode. Caspase 3 and PARP were rapidly cleaved in response to OM, but apoptosis was only partially inhibited by the caspase 3 inhibitor DEVD-CHO. OM also induced an early lysosomal destabilization which increased progressively and was correlated with a parallel increase in apoptotic cells. The cysteine protease inhibitor E64d gave strong protection against apoptosis thus proving the involvement of lysosomal enzymes in OM-induced apoptosis whereas, it did not impede the caspase 3 cleavage. Instead ZVAD-fmk, a general caspase inhibitor, also able to inhibit cathepsin activity, protected cells completely from OM-induced apoptosis. It therefore seems that both caspases and cysteine cathepsins are involved in the execution stage of OM-induced apoptosis.
Omeprazole induces apoptosis in Jurkat cells
SCARINGI, Lucia;CORNACCHIONE, Paola;AYROLDI, Emira Maria;CORAZZI, Lanfranco;CAPODICASA, Enrico;ROSSI, Ruggero;MARCONI, Pierfrancesco
2004
Abstract
We report for the first time a potent apoptotic effect of omeprazole (OM). Apoptosis was induced in Jurkat cells in a time and concentration-dependent mode. Caspase 3 and PARP were rapidly cleaved in response to OM, but apoptosis was only partially inhibited by the caspase 3 inhibitor DEVD-CHO. OM also induced an early lysosomal destabilization which increased progressively and was correlated with a parallel increase in apoptotic cells. The cysteine protease inhibitor E64d gave strong protection against apoptosis thus proving the involvement of lysosomal enzymes in OM-induced apoptosis whereas, it did not impede the caspase 3 cleavage. Instead ZVAD-fmk, a general caspase inhibitor, also able to inhibit cathepsin activity, protected cells completely from OM-induced apoptosis. It therefore seems that both caspases and cysteine cathepsins are involved in the execution stage of OM-induced apoptosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
