TAXOL CYTOTOXICITY ON HUMAN LEUKEMIA-CELL LINES IS A FUNCTION OF THEIR SUSCEPTIBILITY TO PROGRAMMED CELL-DEATH

Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilize s tubulin polymers, increasing the fraction of cells in the G2 or M ph ase of the cell cycle. We report that treatment of HL-60 and U937 myel oid cell lines with 1-10 mu M taxol induces DNA fragmentation and the appearance of morphological features consistent with the process of ap optosis. Taxol-induced apoptosis is inhibited neither by cycloheximide nor by actinomycin D and therefore appears to be independent of new p rotein synthesis. Taxol causes arrest in the G2 phase of the cell cycl e and affects cell viability but does not induce DNA fragmentation in the K562 erythromyeloid cell line. Protein-synthesis inhibitors, colce mid, ionomycin, and starvation, known to trigger apoptosis, proved ine ffective as well. These results suggest that the antineoplastic effect of taxol is mediated in susceptible cell lines by induction of the ap optotic machinery and that K562 partial resistance may depend upon the intrinsic inability of these tumor cells to undergo apoptosis.