Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion.
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.
Keum
Young-Sam
YS
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea.
Han
Seong Su
SS
Chun
Kyung-Soo
KS
Park
Kwang-Kyun
KK
Park
Jeong-Hill
JH
Lee
Seung Ki
SK
Surh
Young-Joon
YJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002273:Carcinogens; D036145:Ginsenosides; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; C097367:ginsenoside Rg3; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D009955:Ornithine Decarboxylase; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate