Recent experiments revealed that prostaglandin-E2 (PGE2) activates nonselective cation channels in enucleated human erythrocytes, leading to Ca2+ entry followed by cell shrinkage, stimulation of sphingomyelinase and ceramide formation, activation of a Ca2+-sensitive scramblase and phosphatidylserine (PS) exposure at the cell surface. PS exposure and cell shrinkage are hallmarks of nucleated cell apoptosis. The present study was performed to explore whether PGE2 may similarly induce apoptosis of nucleated cells through activation of cation channels and to possibly identify the ion channels involved. To this end, K562 human leukaemia cells stimulated with PGE2 exhibit an increased Ca2+ activity as estimated by flow cytometry from Fluo3 fluorescence leading to caspase activation. In parallel, PGE2 induced DNA fragmentation and PS exposure as revealed by FITC-annexin V binding. Gene silencing of Ca2+-permeable TRPC7 channels by RNA interference significantly blunted PGE2-induced DNA fragmentation and triggering of PS exposure. In conclusion, K562 cells express Ca2+-permeable TRPC7 cation channels which are activated by PGE2 and participate in the triggering of apoptosis.