Krebswissenschaft und -therapie

From Normal Cells to Malignancy: Distinct Role of Pro-inflammatory Factors and Cellular Redox Mechanisms

Abstract

Rajendra K Singh, Akulapalli Sudhakar and Bal L Lokeshwar

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 downregulation of antioxidant defense mechanism of cells are emerging major causes of neoplastic transformation and the progression of many solid cancers. The Longer the inflammation persists, higher the risk of developing many age related malignancies such as organs of colon, stomach and prostate etc. 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 exceed the limit of the cells ability to neutralize it. Chronic inflammatory conditions may activate a variety of pro-tumorigenic activities, such as stimulation of proliferative pathway, chemotactic activity, increased invasive potential of cells and angiogenesis. However, many of the antioxidant or cellular redox molecules play a crucial role in maintaining cellular homeostasis and response to oxidative damage but down-regulation of some of the 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) making cells susceptible to 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.