TY - JOUR T1 - Caffeic Acid Phenethyl Ester and Curcumin: A Novel Class of Heme Oxygenase-1 Inducers JF - Molecular Pharmacology JO - Mol Pharmacol SP - 554 LP - 561 DO - 10.1124/mol.61.3.554 VL - 61 IS - 3 AU - G. Scapagnini AU - R. Foresti AU - V. Calabrese AU - A. M. Giuffrida Stella AU - C. J. Green AU - R. Motterlini Y1 - 2002/03/01 UR - http://molpharm.aspetjournals.org/content/61/3/554.abstract N2 - Heme oxygenase-1 (HO-1) is a redox-sensitive inducible protein that provides efficient cytoprotection against oxidative stress. Curcumin, a polyphenolic natural compound that possesses anti-tumor and anti-inflammatory properties, has been reported recently to induce potently HO-1 expression in vascular endothelial cells (Free Rad Biol Med 28:1303–1312, 2000). Here, we extend our previous findings by showing that caffeic acid phenethyl ester (CAPE), another plant-derived phenolic agent, markedly increases heme oxygenase activity and HO-1 protein in astrocytes. The effect seems to be related to the peculiar chemical structures of curcumin and CAPE, because analogous antioxidants containing only portions of these two molecules were totally ineffective. At a final concentration of 30 μM, both curcumin and CAPE maximally up-regulated heme oxygenase activity while promoting marked cytotoxicity at higher concentrations (50–100 μM). Similar results were obtained with Curcumin-95, a mixture of curcuminoids commonly used as a dietary supplement. Incubation of astrocytes with curcumin or CAPE at concentrations that promoted maximal heme oxygenase activity resulted in an early increase in reduced glutathione followed by a significant elevation in oxidized glutathione contents. A curcumin-mediated increase in heme oxygenase activity was not affected by the glutathione precursor and thiol donorN-acetyl-l-cysteine. These data suggest that regulation of HO-1 expression by polyphenolic compounds is evoked by a distinctive mechanism which is not necessarily linked to changes in glutathione but might depend on redox signals sustained by specific and targeted sulfydryl groups. This study identifies a novel class of natural substances that could be used for therapeutic purposes as potent inducers of HO-1 in the protection of tissues against inflammatory and neurodegenerative conditions. ER -