TAXOL INDUCES INTERNUCLEOSOMAL DNA FRAGMENTATION ASSOCIATED WITH PROGRAMMED CELL-DEATH IN HUMAN MYELOID-LEUKEMIA CELLS

The present results demonstrate that the exposure of human myeloid leukemia HL-60 and KG-1 cells to clinically achievable concentrations of taxol produced internucleosomal DNA fragmentation of approximately 200 base-pair multiples, and the morphologic changes characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Taxol-induced PCD was associated with a marked inhibition of suspension culture growth and clonogenic survival of HL-60 cells. In addition, taxol treatment decreased BCL-2 oncogene expression, which is known to block PCD. The exposure to taxol moderately decreased c-myc expression, but did not induce c-jun expression-which has been previously noted for a variety of DNA interactive, antileukemic drugs. These findings indicate that taxol may induce leukemic cell death partly by the alternative but gene-directed and active mechanism of PCD.