Abstract 4615: Quercetin increases the bioavailability and decreases methylation of green tea polyphenols in SCID mice and in A549 lung cancer, 786-O renal cancer and HepG2 liver cells
Authors: Wang Piwen , Heber David , Henning Susanne M. 
Published: June 2012

Green tea polyphenls (GTPs) are metabolized through extensive methylation which reduces their chemopreventive potential. Previously we found that more than 50 percent of (−)-epigallocatechin-3-gallate (EGCG) was methylated to 4″-O-methyl EGCG in mouse tissues and in human prostate after green tea consumption. Methylation significantly decreased the antiproliferative effects of EGCG in prostate cancer cells. Quercetin (Q) is a natural inhibitor of multidrug resistance proteins and catechol-O-methyltransferase (COMT), which determines the absorption and the methylation of GTPs. In order to determine whether co-treatment with Q will increase the bioavailability and decrease the methylation of GTPs in cell culture and mouse tissues, three different human cancer cell lines with different COMT activity were studied in vitro. COMT activity was lowest in lung cancer A549 cells, intermediate in kidney cancer 786-O cells, and highest in liver cancer Hep G2 cells. Corresponding to the COMT activity, A549 cells showed the highest cellular content of EGCG and lowest methylation rate (66.1 pmol/mg cytosolic protein and 63% methylation rate); followed by 786-O cells (39.6, 97% methylated) and Hep G2 cells (25.1, 98% methylated) when incubated with 80 μmol/L EGCG for 2h. Treatment with Q and EGCG increased cellular absorption of EGCG most in A549 cells (4-fold) with decreased methylation rate (19%), less in 786-O cells (2- fold) and decreased methylation rate (56%), while there was little effect on methylation in HepG2 cells. The strongest additive effect was observed on proliferation of A549 cells, followed by renal 786-O cells, and least in Hep G2 cells. In order to examine the impact of Q treatment on GTP bioavailability in vivo, two groups of SCID mice (n=5) fed the AIN-93G diet were provided with brewed tea (one Celestial Seasonings authentic green tea bag brewed in 240ml boiling water for 5min) in drinking water and either diet alone or diet supplemented with 0.4% Q for 2 weeks. Demonstrating the impact of Q on bioavailability and methylation in vivo there was a 2-3 fold increase of non-methylated EGCG and other GTPs observed in lung and kidney tissues. In vivo but not in vitro, the levels of methylated Q increased markedly suggesting that Q acted as a substrate for methylation sparing the GTPs and increasing unmethylated GTPs. These observations demonstrate that Q inhibits methylation of GTPs and when used in combination with GTPs may increase bioavailability. Studies are underway in SCID mice with prostate cancer xenografts to determine whether this increased bioavailability will translate to an enhanced chemopreventive activity.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4615. doi:10.1158/1538-7445.AM2011-4615