The chemopreventive activity of chlorogenic acid is mediated by inhibiting AP-1-MAPKs pathway and inducing phase II detoxifying enzyme through stimulating Nrf2 signaling.
Cancer Epidemiol Biomark Prev 2004 Nov; 13(11)(Part 2)(Suppl):1880S
Chlorogenic acid, one of the most abundant polyphenols in the human diet, inhibits chemical-induced carcinogenesis in animal studies. However, little is known about the molecular mechanisms through which chlorogenic acid prevents carcinogenesis. In this study, we report that chlorogenic acid inhibited the proliferation of A549 human cancer cells in vitro. Results of soft agar assays indicated that chlorogenic acid suppressed 12-O-tetradecanoylphorbol.13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells in a dose-dependent manner. Pretreatment of JB6 cells with chlorogenic acid blocked UVB- or TPA-induced transactivation of activator protein-1 (AP-1) and NF-kB over the same dose range. At low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2-terminal kinases as well as mitogen-activated protein kinase (MAPK) kinase 4 Induced by UVB/TPA, while higher doses are required to inhibit p38 kinase and extracellular signal-regulated kinase Chlorogenic acid also increases the enzymatic activity of glutathione S-transferases (GST). Further study indicated that GST induction by Chlorogenic acid may be through stimulating the nuclear translocation of NF-E2-related factor as well as subsequent induction of antioxidant response element (ARE)-mediated GST expression, which may be blocked by inhibition of PI-3 kinase pathway. These results provide the first evidence that chlorogenic acid could protect against environmental carcinogen-induced carcinogenesis and suggest that the chemopreventive effects of chlorogenic acid may be through its up-regulation of cellular antioxidant enzyme and suppression of reactive oxygen species-mediated NF-kB and AP-1-MAPKs activation.
Morphology; Cell-alteration; Cell-biology; Cell-differentiation; Cell-morphology; Cellular-reactions; Molecular-biology; Cancer; Dose-response; Chemical-inhibition; Chemical-reactions; Chemical-synthesis
Abstract; Conference/Symposia Proceedings
Cancer Epidemiology, Biomarkers & Prevention