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

Abstract

Colon cancerEGCG ester iNOS COX-2 A B S T R A C T 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.

Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects – A review

“…EGCG (epigallocatechin-3-gallate), the main catechin in green tea, serves as a cancer chemopreventive agent (lungs, liver, gastrointestinal tract, skin and prostate cancer), as well as antiobesity and cardiovascular protective compound (Khan & Mukhtar, 2010;Klaus, Pultz, Thone-Reineke, & Wolfram, 2005;Yang & Wang, 1993). The antioxidant activity and beneficial health effects of the main polyphenol of green tea, epigallocatechin gallate (EGCG), was enhanced upon conjugation with docosahexaenoic acid (DHA) and the tetraester so formed was able to arrest colon cancer effectively (Zhong, Chiou, Pan, Ho, & Shahidi, 2012). Polymethoxyflavones, the major components of orange peel, have been found to render health benefits, including anti-inflammatory, anti-carcinogenic, anti-viral, antioxidant, anti-thrombogenic and anti-atherogenic properties Lai et al, 2007;Middleton et al, 2000).…”

Omega-3 polyunsaturated lipophenols, how and why?

“…A mixture of EGCG and tetra/penta esters of DHA (1), was evaluated in azoxymethane-induced colonic carcinogenesis mice [31] (oral diet, supplementation in EGCG-PUFA 0.5%). The mixture was able to reduce the total number of colon large colonic aberrant crypt foci (ACF), a predictive biomarker of colorectal cancer.…”

“…One can imagine that they will be highly metabolized, or rapidly eliminated as are most of the polyphenols after oral ingestion. However Zhong et al reported an increased activity of the EGCG-PUFA esters (1) compared to EGCG after oral administration [31]. Liang et al studied the stability of DOX-hyd ALA 24a and DOX-ami-ALA 24b in rat serum [65].…”

Nanocomplex formation between β-lactoglobulin or caseinomacropeptide and green tea polyphenols: Impact on protein gelation and polyphenols antiproliferative activity

“…Similarly, Zhong and co-workers obtained very interesting results by esterifying EGCg to different healthy x-3 fatty acids. These authors have improved the antioxidant, antiviral, antihypertensive and anticancer properties of EGCg by increasing its solubilization, cellular absorption and bioefficacy both in food and biological systems (Zhong, Chiou, Pan, Ho, & Shahidi, 2012;Zhong, Ma, & Shahidi, 2012;.…”