From normal cells to malignancy: Distinct role of pro-inflammatory factors and cellular redox mechanism in human malignancy

Abstract

The genesis of many solid cancers is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of cell cycle, angiogenesis and acquisition of invasive properties. Among a number of factors, the simultaneous existence of chronic inflammatory mechanism and down-regulation of antioxidant defense mechanism of cells emerging a major consequences of neoplastic transformation and the progression of many solid cancers. Longer the inflammation persists, higher the risk of developing many age related malignancies such as organs of colon, stomach and prostate that might results of disregulation of cellular redox mechanism. Concurrent occurrence of these processes that may affects DNA mutations in cells by excessive generation of free radicals, Reactive Oxygen Species (ROS) and other active intermediates that are exceed the limit of cellular ability to by cellular redox antioxidant system. Chronic inflammatory conditions may activate a variety of pro-tumorigenic activities, such as stimulation of proliferative pathway, chemotactic activity, increased invasive potential of cells. However, many of antioxidant or cellular redox molecules play a crucial role in maintaining cellular homeostasis and response to oxidative damage but down-regulation of some cellular molecules of this process may leads to malignant transformation. We provide an overview of the possible mechanism(s) of interaction of pro-inflammatory factors in down-regulating the antioxidant and cellular redox mechanism(s) for the susceptibly of cells to leads carcinogenesis. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules at early stage of human malignancies. © 2011 Singh RK, et al.