Reactive oxygen species in tumor progression

Abstract

The generation of reactive oxygen radicals in mammalian cells profoundly affects numerous critical cellular functions, and the absence of efficient cellular detoxification mechanisms which remove these radicals can result in several human diseases. Growing evidence suggests that reactive oxygen species (ROS) within cells act as second messengers in intracellular signaling cascades which induce and maintain the oncogenic phenotype of cancer cells. ROS are tumorigenic by virtue of their ability to increase cell proliferation, survival, cellular migration, and also by inducing DNA damage leading to genetic lesions that initiate tumorigenicity and sustain subsequent tumor progression. However, it is also known that ROS can induce cellular senescence and cell death and can therefore function as anti-tumorigenic agents. Therefore, the mechanisms by which cells respond to reactive oxygen species depends on the molecular background of cell and tissues, the location of ROS production and the concentration of individual ROS species. Carcinoma cells produce ROS at elevated rates in vitro, and in vivo many tumors appear persistent to oxidative stress. Thus, the finding that a diet rich in antioxidants or the elimination of ROS by antioxidant compounds prevents the development of certain cancers provided the setting for subsequent investigation of the tumorigenic actions of reactive oxygen species. This review outlines the current knowledge on the various roles of ROS in tumor development and progression.

Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma

“…Many studies have shown that ROS-mediated DNA damage can promote oncogenic transformation by increasing mutation rates [33]. In addition to being mutagenic, recent studies have shown that ROS can function as second messengers in signal transduction pathways [34]. These pathways are known to influence various cellular processes such as proliferation, survival, and motility.…”

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

“…Since FR were accused as causal factors in a large number of diseases, these were sometimes referred as ''Free Radical Diseases''. Some of the important diseases and health issues in this category are cancer [61][62][63][64][65][66][67], cardiovascular diseases [68][69][70][71][72][73], atherosclerosis [74][75][76][77][78][79][80][81], neurological disorders [82][83][84][85][86], renal disorders [87][88][89][90], liver disorders [91][92][93], hypertension [50,94,95], rheumatoid arthritis [96,97], adult respiratory distress syndrome, auto-immune deficiency diseases [98,99], inflammation, degenerative disorders associated with aging [100][101][102][103], diabetes mellitus [104][105]…”

Oxidative status in neuroblastoma: a source of stress?

“…Yet, contrary to our hypothesis, which sought to evaluate whether a greater oxidative response correlated with a progressively enlarging tumor, we interestingly observed a greater extent of oxidation stress during the early time intervals than the 6-week time-point. Given the evidence that ROS support tumor growth and progression [15,16], we surmise that at 2 weeks, where oxidative damage is highest, the ROS generated were as a result of a highly proliferative NB cell mass. At 4 and 6 weeks, as the tumor enlarges and develops a necrotic core, subsequent hypoxia ensues, which triggers an elevation of intratumor ROS.…”