Although we did not detect down regulation of pRb expression,

our data show a significant decrease in E2F1 expression under all tested conditions, suggesting that the inhibition of proliferation we observed could be partially related to this pathway. In some cases, the modulation of the expression of genes of interest caused by unmodified EGCG was more pronounced than that achieved by the biotransformed compound; however, cell culture assays often ignore the bioavailability of the compounds in vivo. The literature shows that the systemic bioavailability of EGCG is a limiting factor for its effectiveness in cancer chemoprevention in internal organs ( Yang & Wang, 2011). Orally ingested EGCG has limited systemic bioavailability, with most of it passing through the colon; and the absorbed EGCG is excreted mostly through the bile into the intestine ( Yang & Wang, 2011). AZD2281 datasheet Studies have shown that the serum levels of EGCG, EGC, ECG, and EC in rats 8 h after oral administration of green tea were 0.061, 0.440,

0.018 and 2.6 μM, respectively, demonstrating that the hydrolysed forms of EGCG are more efficiently absorbed and present at higher concentrations in the serum ( Lubet et al., 2007). Based on these findings, although biotransformed EGCG causes less up-regulation of apoptosis-related genes in vitro than unmodified EGCG, the biotransformed compound may be more effective in vivo. Here, we have shown that the biotransformation of green tea extract and EGCG did not alter the beneficial properties of the original compounds LY294002 cell line (low genotoxicity, antiproliferative activity, and up-regulation of pro-apoptotic genes) and improved their bioavailability. The biotransformation of both green tea extract and EGCG significantly increased their antioxidant potential,

as shown by the ORAC and DPPH assays. ORAC assays demonstrated that the antioxidant capacity of green Sclareol tea extract increased by 55% after enzymatic treatment, and that of EGCG increased by 46%. MTT and SRB assays demonstrated that biotransformation did not render the compounds cytotoxic; instead, biotransformation reduced the toxicity of the EGCG sample without altering its antiproliferative effects on the HT29 and PG100 cell lines. Furthermore, biotransformation increased the anti proliferative capacity of the green tea extract. In relation to apoptosis and cell cycle control, our data showed that either native and biotransformed green tea and/or EGCG up regulated the expression of APAF1, CASP8, CDKN1A and FAS; on the other hand we observed a down regulation of CDK2 and 4, bcl2, bcl2L1, E2F1, and c-myc. Importantly, this study has demonstrated the usefulness of the nutrigenomics perspective and tools in evaluating the benefits of biotechnological modifications of natural food molecules. Using this perspective, we have identified methods to improve the nutraceutical potential of one of the most widely consumed beverages – green tea.