Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion

Mutat Res. 2003 Feb-Mar:523-524:75-85. doi: 10.1016/s0027-5107(02)00323-8.

Abstract

Our previous studies demonstrated the anti-oxidant and anti-tumor promotional properties of the methanol extract of heat-processed Panax ginseng C.A. Meyer [Cancer Lett. 150 (2000) 41]. In the present work, we have evaluated anti-inflammatory as well as anti-tumor promoting effects of Rg(3), a major ginsenoside derived from heat-processed ginseng. Pretreatment of dorsal skins of female ICR mice with Rg(3) significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase activity and 7,12-dimethylbenz[a]anthracene-initiated papilloma formation. In another experiment, Rg(3) pretreatment abrogated the expression of cyclooxygenase-2 in TPA-stimulated mouse skin. Rg(3) also inhibited the TPA-induced activation of the eukaryotic transcription factor, NF-kappaB in both mouse skin and cultured human pro-myelocytic leukemia (HL-60) cells. Moreover, Rg(3) exerted potent inhibitory effects on the activation of another transcription factor, activator protein-1 (AP-1) that is responsible for c-jun and c-fos oncogenic transactivation. Based on these findings, it is likely that the anti-tumor promoting activity of Rg(3) is mediated possibly through down-regulation of NF-kappaB and AP-1 transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinogens / pharmacology*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Curcumin / pharmacology
  • Cyclooxygenase 2
  • Female
  • Gene Expression Regulation / drug effects*
  • Ginsenosides / isolation & purification
  • Ginsenosides / pharmacology*
  • HL-60 Cells
  • Humans
  • Isoenzymes / genetics*
  • Membrane Proteins
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / drug effects
  • NF-kappa B / genetics*
  • Ornithine Decarboxylase / metabolism*
  • Plant Extracts / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Tetradecanoylphorbol Acetate / pharmacology*

Substances

  • Antineoplastic Agents
  • Carcinogens
  • Ginsenosides
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Plant Extracts
  • ginsenoside Rg3
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Ornithine Decarboxylase
  • Curcumin
  • Tetradecanoylphorbol Acetate