title: Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells.
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.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston 29425.
authors.forename: K
authors.initials: K
authors.lastname: Bhalla
authors.forename: A M
authors.initials: AM
authors.lastname: Ibrado
authors.forename: E
authors.initials: E
authors.lastname: Tourkina
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.forename: M E
authors.initials: ME
authors.lastname: Mahoney
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D004273:DNA, Neoplasm / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009707:Nucleosomes / Q000648:ultrastructure*; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D009707:Nucleosomes; D017239:Paclitaxel