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

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.

• Authors: Young-Sam Keum, Seong Su Han, Kyung-Soo Chun, Kwang-Kyun Park, Jeong-Hill Park, Seung Ki Lee, Young-Joon Surh
• Journal: Mutation research (Mutat Res) 2003 Feb-Mar Vol. 523-524 Pg. 75-85 ISSN: 0027-5107 [Print] Netherlands
• PMID: 12628505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Elsevier Science B.V.

Chemical References

• 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

Topics

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