Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells

Leukemia. 1993 Apr;7(4):563-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Northern
  • DNA, Neoplasm / drug effects*
  • Gene Expression / drug effects
  • Genes, jun / drug effects
  • Genes, myc / drug effects
  • Humans
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / pathology
  • Nucleosomes / ultrastructure*
  • Paclitaxel / pharmacology*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Nucleosomes
  • Paclitaxel