Tannic acid potently inhibits tumor cell proteasome activity, increases p27 and bax expression, and induces G(1) arrest and apoptosis

Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers, although the involved molecular target remains unknown. In addition, prote asome inhibitors have been shown to suppress human tumor growth in nude mic e. Most recently, we have reported that ester-bond-containing tea polypheno ls are potent proteasome inhibitors in vitro and in vivo. We have hypothesi zed that TA, which contains multiple similar gallate moieties linked by est er bonds, should inhibit the proteasome activity. Here, we report that inde ed TA potently and specifically inhibits the chymotrypsin-like activity of purified 20S proteasome (IC50 = 0.06 mug/ml), 26S proteasome of Jurkat T-ce ll extracts, and 26S proteasome of living Jurkat cells. Inhibition of the p roteasome by TA in Jurkat cells results in accumulation of two natural prot easome substrates, the cyclin-dependent kinase inhibitor p27(KiP1) and the proapoptotic protein Bax, followed by growth arrest in Gt and induction of apoptotic cell death. Our present study suggests that TA targets and inhibi ts the proteasome in tumor cells, which may contribute to the previously ob served anticarcinogenic activity of TA.