Inhibition of colorectal tumorigenesis in azoxymethane (AOM)-treated rats by green tea polyphenols

A134

The cancer preventive activity of tea and its constituents has been demonstrated in different animal models. However, the results on colon cancer prevention by tea polyphenols in rats have not been consistent. Previously, our results showed that dietary administration of Polyphenon E (PPE, a standardized green tea polyphenol preparation) inhibited the formation of aberrant crypt foci in AOM-treated rats. Herein, we conducted a study with PPE as the preventive agent in the AOM-induced rat colon cancer model using the colorectal tumor as an endpoint. F344 rats were given two weekly injections of AOM (15 mg/kg), and then fed a 20% high fat diet with or without 0.24% PPE for 34 weeks. In the positive control group, 96% of rats developed colorectal tumors with multiplicity of 3.64 ± 0.31, and tumor tissues showed highly elevated levels of Akt and phospho-Akt, and decreased levels of caspase-3 activation, in comparison to the normal colorectal mucosa. Dietary PPE treatment did not change liver or kidney weight, but decreased body weight by 5% in the treated group compared to the control. The decrease in body weight may be due to inhibition of lipid absorption by tea polyphenols (as suggested by our study in a high fat diet-induced obesity mouse model). Dietary PPE treatment significantly decreased tumor multiplicity and tumor size by 55% (p < 0.01) and 45% (p < 0.05), respectively. Moreover, treatment with 0.24% PPE also significantly decreased the incidence of adenocarcinoma (from 61% to 27%, p < 0.05), the multiplicity of adenoma (by 45%, p < 0.05), and the multiplicity of adenocarcinoma (by 80%, p < 0.01). Dietary PPE treatment significantly increased the levels of major tea polyphenols, i.e., EGC, EC, EGCG and ECG, in both plasma and colorectal mucosa of treated rats. Our results also showed that PPE treatment decreased levels of PGE2, LTB4 and 8-isoprostane in plasma of treated rats. Taken together, we demonstrated convincingly the inhibition of rat colon carcinogenesis by dietary treatment with green tea polyphenols. (Supported by NIH grant CA88961).