Abstract A59: Combination of quercetin and tannic acid as a potential proteasome inhibitor for cancer chemoprevention

Abstract

Abstract To look for oral proteasome inhibitors, the daily food is best source for cancer chemoprevention. A combination of active components from vegetables, coffee, tea, and fruit could be more efficient to inhibit 26S proteasome activities for preventing cancer diseases. Tannic acid and quercetin have been shown to strongly inhibit 26S proteasome activity, but the molecular target involved remains unknown. Overlay assay, peptide assay, western blot, and 2-D gels were used to assess the combination of quercetin and tannic acid as a potential inhibitor. Here, we demonstrated that the combination of quercetin and tannic acid synergistically suppresses chymotrypsin-like, caspase-like, and trypsin-like proteolytic activities and are tightly binding substrates. Quercetin plus tannic acid do not perturb the proteasome structure, inhibit the 26S proteasome affected by ubiquitin, ATP, or β-casein, and inhibit β-casein degradation by the 26S proteasome in vitro. Finally, inhibition of the proteasome by a combination of quercetin and tannic acid in Hep-2 cells resulted in induction of S5a at low dose, accumulation of ubiquitin, and the cleavage of pro-caspase-3, followed by induction of apoptotic cell death. Evaluating the combination of quercetin and tannic acid as an oral drug to prevent cancer may provide a pharmacological rationale to pursue preclinical trials of this combination. Citation Format: Tsui-Ling Chang, Chi-Hsien Wang. Combination of quercetin and tannic acid as a potential proteasome inhibitor for cancer chemoprevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A59.