The Effect of Reactive Oxygen Species Threshold on Cancer Cell Fate

There has been an argument going on for theeffectiveness of dietary supplements includingvarious vitamins enriched in antioxidants in cancertreatment and prevention. Several trials have shownthat vitamins are unable to suppress cancerprogression and may even promote the disease.۱Some other reports suggest that antioxidants mayeven accelerate cancer progression, in line with theirdrug resistance function.۲A classical model of carcinogenesis states thatfree radicals can act as promoters of cancerinitiation, promotion and progression phases. In the ۳initiation phase where lethal mutations are absent,free radicals contribute to cell transformation andcancer initiation by generating ROS (reactiveoxygen species) such as lipid peroxides that inducemutations and damage DNA. An equilibrium exists ۴between growth and death in normal cells; however,this balance is disturbed in cancer cells and freeradicals act in favor of cell survival/growth byabrogating programmed death and tumorsuppressing activities.In the promotion phase that includes clonalexpansion, free radicals act as second messengers tocontrol cancer cell proliferation and differentiation.Intracellular concentrations of ROS are critical inthis phase as they determine if ROS can induceapoptosis or growth. In the progression phase of ۵carcinogenesis that includes epithelial-tomesenchymaltransition and development ofangiogenesis, ROS play important roles bymediating crosstalk between integrins as key playersof cell proliferation, survival, and migration on theone hand and many cytokines and growth factors onthe other hand.