Models of reactive oxygen species in cancer

Abstract

Increased generation of reactive oxygen species (ROS) has been observed in cancer, degenerative diseases, and other pathological conditions. ROS can stimulate cell proliferation, promote genetic instability, and induce adaptive responses that enable cancer cells to maintain their malignant phenotypes. However, when cellular redox balance is severely disturbed, high levels of ROS may cause various damages leading to cell death. The studies of ROS effects on biological systems, their underlying mechanisms and therapeutic implications largely depend on proper experimental models. Here we review several in vitro and in vivo models for ROS research.

Antioxidant Role of p53 and of Its Target TP53INP1

“…Mouse models of oxidative stress were recently reviewed, illustrating several cases where inactivation of one antioxidant enzyme promotes cancer development [57,58]. In addition, these reviews underscore other transcription factors than p53, such as JunD, FoxOs, Bmi1, and HIF-2α, also involved in the modulation of antioxidant enzymes expression.…”

Oxidative Therapy Against Cancer

“…High levels of oxidative stress have been found in cancer patients (McEligot et al, 2005;Lu et al, 2007), and it has been reported that different biomarkers of oxidative-stress-mediated events are elevated in cancer-prone tissues (Bartsch and Nair, 2000). In vitro studies clearly show that human tumor cell lines produce ROS at a much higher rate than non-transformed cells (Oberley and Buettner, 1979;Lu et al, 2007). In cancerous cells, a high level of oxidative stress is observed, which may result not only from the overproduction of ROS, but also from low levels or inactivation of antioxidants .…”

“…Many reports suggest that cancer cells are under a continuous oxidative stress (Pervaiz and Clement, 2004;Schumacker et al, 2006;Kryston et al, 2011). Studies with human tumor cell lines clearly show that these cells produce ROS at a much higher rate than healthy cells (Oberley and Buettner, 1979;Lu et al, 2007). ROS have been established as important molecules involved in the multistage process of carcinogenesis (Klaunig and Kamendulis, 2004).…”

The Regulation of Aging and Longevity: A New and Complex Role of p53

“…Increased intracellular ROS levels and loss of antioxidant defense pathways in cells have been shown to result in cancer and aging. [88][89][90][91][92] However, some recent studies have raised questions challenging the role of oxidative stress and ROS in aging. 93 Recent studies have shown that p53 can exert both pro-oxidant and antioxidant functions in cells depending on the type and extent of stress signals that activate p53 (Figure 3), which could be a potential mechanism accounting for the dual activities of p53 in both promoting and preventing aging.…”