These results show that the tested concentrations of EGCG were not genotoxic, meaning that they did not induce any significant DNA damage in the tested cells. Biotransformation of EGCG with tannase did not alter these results. In summary, our data show that unmodified and biotransformed green tea extracts and EGCG were neither cytotoxic nor genotoxic. Furthermore, we observed that the antioxidant and anti-proliferative capacities of these compounds were significantly increased by enzymatic intervention. Due to the potential cancer selleck chemical chemopreventive mechanisms of green tea and EGCG include prevention of DNA damage (Malhomme de la Roche et al., 2010 and Morley et al., 2005),

inhibition of inflammatory processes, decreased angiogenesis, and antiproliferative/pro apoptotic effects (Shimizu et al., 2011 and Yang and Wang, 2011), we used the Human Cancer Pathway

Finder Array to evaluate the effects of unmodified and biotransformed green tea extract and EGCG on the expression profiles of 84 genes representative of the six biological pathways involved in transformation and tumorigenesis. Treatment with either unmodified or biotransformed green tea extract significantly changed the expression of 14% of the tested genes (12/84), whereas treatment with either unmodified or biotransformed EGCG altered the pattern of expression of 17% (14/84) of the genes. The statistically significant and biologically relevant results are shown in Table 4. The gene expression values presented were obtained by normalising expression levels to those Bortezomib molecular weight observed in the control cells. In relation to apoptosis and cell cycle control, our data showed that APAF1 (apoptotic peptidase activating

factor 1), CASP8 (caspase 8, apoptosis-related cysteine peptidase), CDKN1A (cyclin-dependent kinase inhibitor 1A), and FAS (TNF receptor superfamily member 6) were up regulated by biotransformed green tea extract, unmodified Adenosine triphosphate EGCG and biotransformed EGCG. We also observed a down regulation of CDK2 and 4 (Cyclin-dependent kinase 2 and 4), bcl2 (B-cell CLL/lymphoma 2), bcl2L1 (BCL2-like-1), E2F1 (E2F transcription factor 1), and c-myc (V-myc myelocytomatosis viral oncogene homologue) (Table 4). APAF1, CASP8 and CDKN1 are closely related to the caspase enzyme family. Some of these genes encode members of the caspase family of proteases, whereas others encode proteins responsible for caspase activation. In either case, these proteins contribute to the initiation of the caspase cascade that commits the cell to apoptosis (Gramantieri et al., 2005, Jones et al., 2011 and Yang et al., 2006). The protein encoded by the FAS gene is a member of the TNF-receptor superfamily. This superfamily includes FAS, CD40, CD27, and RANK. FAS contains a death domain, and the interaction of this receptor with its ligand allows the formation of a death-inducing signalling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10.