Taxotere activates transcription factor AP-1 in association with apoptotic cell death in gastric cancer cell lines

Anticancer Res. Nov-Dec 1999;19(6B):5399-405.

Abstract

We investigated whether a novel mitotic inhibitor, taxotere can activate the transcription factor AP-1 in association with apoptotic cell death in 8 gastric cancer cell lines. Apoptotic cell death was analyzed by DNA ladder formation assay, and AP-1 binding activity was assessed by gel mobility-shift assay. The activation of AP-1 binding was induced in accordance with the sensitivity to taxotere in gastric cancer cell lines. The relationship between the increase of AP-1 binding and the formation of internucleosomal DNA ladders induced by taxotere was significant (p < 0.05). Furthermore, the activation of AP-1 binding was induced following the treatment of taxotere in a dose and -time dependent manner. Although the sensitivity to taxotere was correlated with the formation of internucleosomal DNA ladders in apoptotic cell death, its sensitivity was not influenced by their p53 genomic states in gastric cancer cell lines. Rather, the activation of AP-1 binding was correlated with the induction of a growth arrest and DNA damage inducible gene, gadd153 (p < 0.05). These results indicate that the activation of AP-1 binding by taxotere seems to be an important factor in determining its sensitivity in association with internucleosomal DNA ladders, and suggest that the induction of gadd153 gene could be a downstream target of AP-1-regulated genes involved in signal transduction pathways leading to apoptosis in gastric cancer cells.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins*
  • DNA Primers
  • DNA, Neoplasm / metabolism
  • DNA-Binding Proteins / genetics
  • Docetaxel
  • Genotype
  • Humans
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology
  • Protein Binding
  • Stomach Neoplasms / pathology*
  • Taxoids*
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factor CHOP
  • Transcription Factors / genetics
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • CCAAT-Enhancer-Binding Proteins
  • DDIT3 protein, human
  • DNA Primers
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Taxoids
  • Transcription Factor AP-1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Transcription Factor CHOP
  • Docetaxel
  • Paclitaxel