Paclitaxel-induced apoptosis in Jurkat, a leukemic T cell line, is enhanced by ceramide

We hypothesized that the lipid second messenger, ceramide, and microtubule- directed chemotherapeutic agents might engage converging pathways in induci ng apoptosis. Our studies demonstrated that simultaneous treatment of Jurka t cells with paclitaxel and ceramide enhanced paclitaxel-induced cell growt h inhibition. Cell cycle analysis indicated a significant increase in the h ypodiploid population over that observed with paclitaxel treatment alone. M orphologic evaluation and a TUNEL assay confirmed a dramatic increase in ap optosis in Jurkat cells treated with the combination of these two agents. T his is the first demonstration that paclitaxel and ceramide interact in a s upra-additive manner to decrease leukemic T-cell growth, suggesting a possi ble application of paclitaxel and ceramide in combination therapy. (C) 1999 Elsevier Science Ltd. All rights reserved.