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Induction of phase II detoxifying enzymes and inhibition of AP-1-MAPKS pathway by natural antioxidant chlorogenic acid.
Ding-M; Feng-RT; Bowman-L; Lu-Y; Castranova-V
Free Radic Biol Med 2004 Jan; 37(Suppl 1):S34
Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet. The antioxidant and anticarcinogenic properties of chlorogenic acid have been established in animal studies. However, little is known about the molecular mechanisms through which chlorogenic acid inhibits 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 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 AP-1 and NF-fUB over the same dose range. At low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2-terminal kinases as well as MAPK kinase 4 (MKK4) induced by UVB/TPA, while higher doses are required to inhibit p38 kinase and extracellular signal-regulated kinases. Chlorogenic acid also increases the enzymatic activity of glutathione S-transferases (GST) as well as that of antioxidant response element (ARE)-mediated induction of a luciferase reporter. Further study indicated that chlorogenic acid stimulates the nucleus translocation of NF-E2-related factor (Nrf2). 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 enzymes and suppression of ROS-mediated NF-fUB and AP-1-MAPKs activation.
Enzymes; Detoxifying-agents; Detoxification; Antioxidants; Antioxidation; Acids
Abstract; Conference/Symposia Proceedings
Free Radical Biology and Medicine
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