Protective effects of epigallocatechin gallate (EGCG) derivatives on azoxymethane-induced colonic carcinogenesis in mice

Epigallocatechin gallate (EGCG), the major polyphenol in green tea and a functional food ingredient/nutraceutical with health-promoting properties, was structurally modified by esterification with butyric and docosahexaenoic (DHA) acid in order to improve its lipophilicity and hence bioefficacy in vivo. The lipophilic derivatives of EGCG so-prepared were evaluated for their anticancer activity against azoxymethane (AOM)-induced colon carcinogenesis in mice. Formation of colonic aberrant crypt foci (ACF) was monitored as the biomarker of colorectal cancer (CRC). It was found that oral administration of EGCG derivatives led to reduced size of ACF in the mouse colon. EGCG–DHA esters were more effective than EGCG-butyrate in inhibiting the formation of ACF. The total number of large colonic ACF was remarkably decreased by treatment with EGCG derivatives, especially by the EGCG–DHA esters, which showed a 100% inhibition of large ACF formation. Two tumor-promoting enzymes, iNOS and COX-2 were also inhibited by EGCG derivatives to various extents at the expression level. The results suggest that the lipophilic ester derivatives of EGCG are effective in inhibiting colon carcinogenesis and may be good candidates for colon cancer prevention/treatment.

► EGCG esters were prepared by esterification of EGCG with butyric acid and DHA.
► Oral administration of EGCG esters led to reduced size of ACF in the mouse colon.
► EGCG esters remarkably decreased the total number of colonic tumors in mice.
► EGCG esters inhibited expression of two tumor-promoting enzymes, iNOS and COX-2.