Moos Philip J, Edes Kornelia, Mullally James E, Fitzpatrick Frank A
Department of Oncological Sciences and Department of Medicinal Chemistry, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
Carcinogenesis. 2004 Sep;25(9):1611-7. doi: 10.1093/carcin/bgh163. Epub 2004 Apr 16.
Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.
