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 ability of a hydrolyzable tannin, gallotannin (GT), and a condensed tannin extracted 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 treatment with DMH for 24 weeks. Alternatively, mice were given tannins by intraperitoneal 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 were significantly inhibited by GT and RA in the above treatment regimens. The most effective treatments included GT by gavage, RA bark extract by intraperitoneal injection, and either tannin dissolved in drinking water. Extent of inhibition of ACF 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 half-maximal inhibition estimated to be 20 micrograms/ml. The treatment was not cytotoxic to cells at 1-40 micrograms/ml. Interestingly, at 10 micrograms/ml, GT induced apoptosis in T-84 cells as determined by the Hoechst DNA staining technique. Collectively, these findings support a potential role for tannins as chemopreventive agents against colon cancer.
Gali-Muhtasib
H U
HU
Department of Biology, American University of Beirut, Beirut, Lebanon. amro@aub.edu.lb
Younes
I H
IH
Karchesy
J J
JJ
el-Sabban
M E
ME
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D004333:Drug Administration Routes; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D013634:Tannins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D013634:Tannins; D019813:1,2-Dimethylhydrazine