Omeprazole induces apoptosis in jurkat cells.
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.
Department of Clinical and Experimental Medicine, General Pathology and Immunology Section, General Hospital, University of Perugia, Perugia, Italy. scaringi@unipg.it
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Scaringi
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Cornacchione
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Ayroldi
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Corazzi
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Capodicasa
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Rossi
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Marconi
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D019169:Jurkat Cells; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D007202:Indicators and Reagents; D004247:DNA; D020169:Caspases; D009853:Omeprazole