ABSTRACT
The term “oxidative stress” refers to a significant imbalance between oxidant production and antioxidant defenses. Reactive oxygen species (ROS) are formed constantly as byproducts of energy generation, inflammation, or as participants in redox signaling. The formation of ROS is accelerated during increased energy metabolism such as during exercise, obesity, cell proliferation, and cancer cell growth. Depending on the concentration, ROS contribute to initiation and progression of cancer development. At higher concentrations, however, ROS can induce cell cycle arrest or cell death of cancer cells. The presence of ROS stimulates a complex system of antioxidants that counterbalances oxidative stress. The antioxidant network consists of a large variety of dietary compounds such as vitamins, bioactive phytochemicals with highest concentration in fruits, nuts, and vegetables. In addition, endogenous metabolic products and antioxidant enzymes that can be triggered by redox regulated transcription factors contribute to the antioxidant network. The ability of antioxidants to accept and donate electrons also enables them to act as pro-oxidants under certain conditions and causing oxidative damage to biomolecules. Whether these pro-oxidant properties are physiologically relevant in vivo is unclear. Preclinical and epidemiological studies as well as meta-analyses provide evidence that increased intake of dietary lipophilic and hydrophilic antioxidants such as vitamin E, carotenoids, flavonoids, and vitamin C reduce total cancer incidence and mortality. Evidence from clinical intervention trials, however, is mixed. Based on the potential to form ROS, some antioxidants such as vitamin C have been tested in cancer treatment when injected intravenously. Several clinical studies are ongoing using pro-oxidants individually or in combination with chemotherapeutic compounds.
