protein metabolism Also, we found that EIF3K was down regulated in vita min C treated AGS cells. A previous study has been reported that the down regulation of eIF3k attenuating apoptosis in simple epithelial cells. Tumor Necrosis Factor Alpha Induced Protein 3 or TNFAIP3 is a novel tumor suppressor protein and a key player in the negative feedback regulation of NF kB signaling in response to multiple GSK-3 stimuli. TNFAIP3 also regulates TNF induced apoptosis. Moreover, TNFAIP3 induces cell growth arrest and apoptosis, ac companied by down regulation of nuclear factor kappa B activation. Presently, TNFAIP3 was up regulated in vitamin C treated AGS cells. Figure 5 represents the overview of the growth inhibition effect of vitamin C on AGS cells and protein expression pat terns.

These proteomic results reveal that vitamin C inhibited cell growth, and apoptosis related proteins were involved in promoting and regulating cell death in AGS cells. Conclusions In summary, vitamin C showed strong inhibitory effect on AGS cell growth at pharmacological concentrations, and 20 differentially expressed proteins were identified in AGS cells after exposure to vitamin C by using 2 DE and MADLI TOF analysis. In particular, proteins involved in signal transduction 14 3 3��, 14 3 3�� and 14 3 3, and cytoskeletal proteins tropomyosin alpha 3 chain and tropomyosin alpha 4 chain were down regulated, Peroxiredoxin 4 was up regulated in vitamin C treated AGS cells compared with the control. Further, the expressions of 14 3 3 isoforms were verified with a Western blot analysis.

The findings of this study suggest that vitamin C could inhibit AGS cell growth, alter the apoptosis re lated proteins, and might be helpful to understand the molecular mechanism of vitamin C s anti tumor effect in AGS cells. Currently, it is possible to observe the activity of almost all molecules of a given type in a single screen using high density chips, or sequencing related techniques. Lately, the number of studies using microarray platforms for analysis of mRNA are quickly being followed by similar analyses related to miRNAs. Only recently both types of variables were analyzed simultaneously, while, typically, both types of data are analyzed in search for molecules sharing similarity, using simply the expression available at the time e. g.

clustering and association networks or similarity with or dependency from other types of traits, providing for example clinical classes or other non molecular informa tion on the samples i. e. Signif icant Analysis of Microarray, Gene Set Enrichment Analysis. However, this approach implies to analyze separately different aspects of a system and the results may not be concordant with analyses of the system as a whole. For example, interactions among miRNAs and mRNAs may be underestimated or comple tely overlooked. This lack of information can be expressed as missing the emergent properties of the system. While the concept of emergent properties is well known in S