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 inducing apoptosis. Our studies demonstrated that simultaneous treatment of Jurkat cells with paclitaxel and ceramide enhanced paclitaxel-induced cell growth inhibition. Cell cycle analysis indicated a significant increase in the hypodiploid population over that observed with paclitaxel treatment alone. Morphologic evaluation and a TUNEL assay confirmed a dramatic increase in apoptosis in Jurkat cells treated with the combination of these two agents. This is the first demonstration that paclitaxel and ceramide interact in a supra-additive manner to decrease leukemic T-cell growth, suggesting a possible application of paclitaxel and ceramide in combination therapy.
Myrick
D
D
Department of Pathobiology, Brown University, Providence, RI, USA.
Blackinton
D
D
Klostergaard
J
J
Kouttab
N
N
Maizel
A
A
Wanebo
H
H
Mehta
S
S
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002518:Ceramides / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D002518:Ceramides; D017239:Paclitaxel