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White Tea/Sulindac Chemopreventive Mouse Colon Ca

#A138 Cancer Chemoprevention by a Combination of White Tea Plus Sulindac in a Mouse Model Expressing an Oncogenic form of â-catenin.

Gayle Orner,1 Wan-Mohaiza Dashwood,1 Niall C. Tebbutt,2 Qingjie Li,1 Joan K. Heath,2 Melinda C. Myzak,1 Matthias Ernst,2

Roderick H. Dashwood.1 Oregon State Univ.,1 Corvallis, OR, Ludwig Institute for Cancer Research,2 Melbourne, Australia.

A33ÄNâ-cat mice contain a truncated, oncogenic version of â-catenin with expression specifically targeted to intestinal epithelial cells.

In contrast to other mice in which the â-catenin signaling pathway has been mutated, A33ÄNâ-cat mice do not develop large numbers of spontaneous tumors, however they are more sensitive to azoxymethane (AOM)-induced colon carcinogenesis than wild-type controls.

AOM-treated A33ÄNâ-cat mice may be particularly appropriate as models for human sporadic colorectal cancer because (as in humans) the tumors are located primarily in the colon, and because susceptibility results from a combination of genetic and environmental factors.

Thus white tea, sulindac, or a combination of white tea plus sulindac were tested in this model of sporadic colon cancer. At 6 weeks of age, male mice were given 5 mg/kg AOM or vehicle by i.p. injection twice a week for 6 weeks.

Beginning one week after the final injection, mice were treated in the drinking water with white tea (1.5%, 2 min brew), 80 ppm sulindac, a combination of 80 ppm sulindac in 1.5% white tea, or buffered water.

Eight weeks treatment with white tea or sulindac alone did not provide significant protection towards tumor multiplicity.

However, A33ÄNâ-cat mice treated with the combination of 1.5% white tea plus 80 ppm sulindac had significantly fewer polyps (P < 0.05) than control mice, or mice given either tea or sulindac alone.

Polyps from sulindac-treated mice had lower levels of â-catenin and target proteins than polyps from control or tea-treated mice.

This research provides evidence that a combination of white tea plus sulindac is effective at inhibiting colon tumors in a mouse model of sporadic cancer, possibly through effects on â-catenin signaling.

(CA80176, CA97485, and a Linus Pauling Institute Pilot Grant).

Frontiers in Cancer Prevention Research, 2003 AACR

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