Plant tannins inhibit the induction of aberrant crypt foci and colonic tumors by 1,2-dimethylhydrazine in mice

We have shown that naturally occurring tannins possess antitumor promotion activity in mouse skin. In the present investigation, we studied the abilit y of a hydrolyzable tannin, gallotannin (GY), and a condensed tannin extrac ted from red alder (RA) bark to inhibit 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF) and tumors in Balb/c mice. In addition, we determined the ability of GT to inhibit the proliferation and to induce apoptosis in a human colon cancer cell line (T-84). Mice were given tannins by intraperitoneal injections, by gavage, or in drinking water before trea tment with DMH for 24 weeks, Alternatively, mice were given tannins by intr aperitoneal injection or gavage for only 2 weeks before DMH administration, then tannin administration was discontinued and mice were treated with DMH for 24 weeks. The multiplicity, size, and distribution of ACF and tumors w ere significantly inhibited by GT and RA in the above treatment regimens. T he most effective treatments included GT by gavage, RA bark extract by intr aperitoneal injection, and either tannin dissolved in drinking water. Exten t of inhibition of A CF and tumors was gender independent. In cell culture experiments, GT treatment for three days inhibited the growth of T-84 cells , with a concentration resulting in ha maximal inhibition estimated to be 2 0 mug/ml. The treatment was not cytotoxic to cells at 1-40 mug/ml. Interest ingly, at 10 mug/ml, GT induced apoptosis in T-84 cells as determined by th e Hoechst DNA staining technique. Collectively, these findings support a po tential role for tannins as chemopreventive agents against colon cancer.