Redox cell signaling genomics and proteomics target place modulators in cancerogenesis: New diagnostic and therapeutic possibilities

Abstract

Summary: Within the complex process of signal transduction through the cell under the influence of external factors, signal transmission is initiated through a specific communication, protein-protein interaction (phosphorylation, dephosphorylation, association, dissociation, oxidation, glycation, nitrosylation, proteolysis), determining the biologic response of the cell. Many of the cellular signal transduction pathways, such as JAKSTAT, MAP, PKC-kinase cascade, NF-kB signal transduction pathway, undergo down regulation mediated by N-acetyl-cystein and reduced glutathione, while the decline of GSH concentration and redox stress initiate their activation. Activated redox signaling pathways are the mediators of mitogenic effects in cancerogenesis. Two types of genes, comprising only a small part of the human cell genome, have a key role in cancerogenesis. Proto-oncogene and tumor suppressor gene dysfunction induce disturbances in the regulation of signal transmission pathways which control the cell cycle, apoptosis, genome stability, differentiation and morphogenesis. Alterations in these important physiologic processes are responsible not only for the initiation and promotion of malignant transformation of the cell, but for further tumor progression as well. Free radicals and their oxidatively modified products induce activation of critical sensory loci in the signal pathway proteoma, controling cellular proliferation, apoptosis and cellular phenotype alteration. Therefore, it is vital to define the therapeutic indications for antioxidants and other modulators of target places of redox cell signaling genomics and proteomics as they are all part of a complex network of multifactorial oncogene collaboration in the process of cancerogenesis.