Inhibitory Effect of Paeoniflorin on Fos-Jun-DNA Complex Formation and Stimulation of Apoptosis in HL-60 Cells

  • Kwon, Hae-Young (School of Chemistry and Molecular Engineering, Seoul National University) ;
  • Kim, Kyoung-Su (School of Chemistry and Molecular Engineering, Seoul National University) ;
  • Park, Se-Yeon (School of Chemistry and Molecular Engineering, Seoul National University) ;
  • Lee, Dug-Keun (National Institute of Health, Bethesda) ;
  • Yang, Chul-Hak (School of Chemistry and Molecular Engineering, Seoul National University)
  • Received : 2000.11.01
  • Accepted : 2000.11.24
  • Published : 2001.01.31

Abstract

The Fos-Jun heterodimers are part of the regulatory network of gene expression and nuclear proteins encoded by proto-oncogenes. The activation of Fos-Jun is important in the transmission of the tumor-promoting signal from the extracellular environment to the nuclear transcription mechanism. To search for the inhibitors of the Fos-Jun DNA complex formation, several natural products were screened and water-soluble paeoniflorin reduced the binding activity of the Fos-Jun heterodimer. This active compound was purified by silica gel column chromatography and HPLC. The electrophoresis mobility shift assay and reverse-phase HPLC test showed that paeoniflorin reduced the AP-l function. The cytotoxic effect of paeoniflorin was observed in HL-60. These results indicate that paeoniflorin blocks the Fos-Jun heterodimer-binding site of the AP-l DNA and it also has cytotoxic effects on human leukemia cell lines.

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