Proteomic analysis revealed that the apoptosis re lated proteins were involved in promoting and regulating cell death of AGS cells. Ascorbic acid is an excellent antioxidant and ascorbate caused toxicity to cancer cells, but had no effect on nor mal cells at the same concentration. In the present study, vitamin C had a strong inhibitory effect on cell www.selleckchem.com/products/ABT-888.html pro liferation of AGS Inhibitors,Modulators,Libraries cells in a dose dependent manner after 24 h treatment with vitamin C, and the IC50 of vitamin C was found approximately 300 ug mL or 1. 7 mM mL. And also, morphological changes were observed in AGS cells, such as cell shrinkage and density in vitamin C treated cells compared with the control cells. This result revealed that vitamin C inhibited AGS cell growth at pharmacological concentrations.

Further, 2 DE gel analysis was performed to study the protein Inhibitors,Modulators,Libraries expres sions in AGS cells due to inhibitory effects of vitamin C. The silver stained gels of control and vita min C treated gels were analyzed by using Progenesis Samespots software, and we found 32 statistically significant differentially expressed protein spots. Finally, 20 differentially expressed proteins were successfully identi fied by MALDI TOF MS analysis using the MASCOT search engine and the SwissProt database. Among GSK-3 20 proteins, six were up regulated and fourteen were down regulated in vitamin C treated AGS cells compared with the control. These proteins are mainly involved in cell mobility, antioxidant and detoxification, signal transduction and protein metabolism.

Vitamin C down regulated proteins involved in the signal transduction, 14 3 3 isoforms Research on cancer targets have determined that 14 3 3 proteins are known to be involved in various biological processes like signal transduction, cell cycle control, apoptosis, cellular metabolism, proliferation, cytoskeletal Inhibitors,Modulators,Libraries regulation, transcription, and redox regulation or stress response. Among these differentially expressed pro teins, three isoforms of 14 3 3 proteins, 14 3 3�� and 14 3 3�� and 14 3 3 were down regulated. The Bad protein, a proapoptotic family member, is one of the targets of 14 3 3 proteins. When Bad disassociated from 14 3 3, the Bad is found localized to the mitochon dria bound to Bcl 2 and Bcl xL, and induced cell death. In addition, vitamin C induced apoptosis by down regulation of 14 3 3�� and dephosphorylation of Bad via a mitochondrial dependent pathway in AGS cells.

Moreover, the remarkable dissociation of Inhibitors,Modulators,Libraries Bad from 14 3 3B is the apoptosis mechanism of vitamin C through the increasing of ER stress and the translocation of Bad to mitochondria after dissociation from 14 now 3 3B in human colon cancer cell line, HCT 8. These findings suggest that Bad dissociated from 14 3 3 is a key mediator in vita min C induced apoptosis through the disruption of mito chondrial membrane potential.