Apoptosis in P388 Leukemia Cells Induced by Specific Inhibitors of 5- and 12-Lipoxygenase and the Product of Cyclooxygenase, Prostaglandin E2

Abstract

We studied the effect of specific inhibitors of 5- and 12-lipoxygenases as well as the product of cyclooxygenase activity, prostaglandin E2, on proliferation and death of P388 leukemia cells. Inhibition of 5- and 12-lipoxygenases in the cells inhibits proliferation and induces apoptosis. The concentrations of baicalein, an inhibitor of 12-lipoxygenase, and AA861, an inhibitor of 5-lipoxygenase, causing a 50% death rate (LC50) proved to be the same, 50 microM. Excessive prostaglandin also inhibited proliferation of the cells and induced apoptosis. The LC50 for prostaglandin E2 was 4 microM. The obtained data suggest that apoptosis in P388 cells after lipoxygenase inhibition can be induced by both deficiency of lipoxygenase products and excess of prostaglandins in the cell.