Inhibitory effects of the ginsenoside Rg₃ on phorbol ester-induced cyclooxygenase-2 expression, NF-κB 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 Rg₃, a major ginsenoside derived from heat-processed ginseng. Pretreatment of dorsal skins of female ICR mice with Rg₃ significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase activity and 7,12-dimethylbenz[a]anthracene-initiated papilloma formation. In another experiment, Rg₃ pretreatment abrogated the expression of cyclooxygenase-2 in TPA-stimulated mouse skin. Rg₃ also inhibited the TPA-induced activation of the eukaryotic transcription factor, NF-κB in both mouse skin and cultured human pro-myelocytic leukemia (HL-60) cells. Moreover, Rg₃ 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 Rg₃ is mediated possibly through down-regulation of NF-κB and AP-1 transcription factors.