**6. Antioxidants and tumorigenesis**

Genetic alterations that promote tumor cause to produce endogenous antioxidants [14]. In this process, Nrf2 is the main factor for the transactivation of involved genes in the maintenance of redox homeostasis [34]. As constitutive upregulation of Nrf2 factor has been reported for a variety of human cancer types, Nrf2 activity has been indicated to be necessary for proliferation of cancer cells [35–37], reprogramming of metabolism [38], chemoresistance [39], serine biosynthesis [36], as well as mRNA translation [37] in part through maintenance of redox homeostasis. Hi-activated pathway of Nrf2 increases the amount of cellular ROS scavengers. On the other hand, lowering stress burden via enhancing detoxifying force can affect the pathways that promote proliferation and growth [40, 41]. Blocking antioxidant activity in cancer cells decreases their ability to balance oxidative insult and might

result in cell death [42]. In addition to Nrf2, the transcription factor p53 has also been shown to suppress ROS accumulation via directly regulating the expression of a variety of antioxidant genes including SOD2, GPX1, and CAT [14, 39] and through the induction of the metabolic TIGAR gene (TP53-inducible glycolysis and apoptosis regulator) [14].

Oxidative stress can happen due to reduction in enzymatic antioxidant activities. Moreover, it can occur due to ionizing, radiation, chemotherapy, aging, shear stress, cytokines, and growth factor receptor interactions [14]. Antioxidants and oxidative stress interact with the initiation, promotion, and progression of cancer [41]. Actually, the cell-damaging effects of free radicals can be balanced by antioxidants. Furthermore, as the fruits and vegetables are good sources of antioxidants, people who eat them more than others have a lower risk for various diseases such as heart and neurological diseases, and there is evidence that some types of vegetables and fruits in general protect against a number of cancers [43].
