Redox Potential of Antioxidants in Cancer Progression and Prevention

Abstract

The benevolent and detrimental effects of antioxidants are much debated in clinical trials and cancer research. Several antioxidant enzymes and molecules are overexpressed in oxidative stress conditions that can damage cellular proteins, lipids, and DNA. Natural antioxidants remove excess free radical intermediates by reducing hydrogen donors or quenching singlet oxygen and delaying oxidative reactions in actively growing cancer cells. These reducing agents have the potential to hinder cancer progression only when administered at the right proportions along with chemo-/radiotherapies. Antioxidants and enzymes affect signal transduction and energy metabolism pathways for the maintenance of cellular redox status. A decline in antioxidant capacity arising from genetic mutations may increase the mitochondrial flux of free radicals resulting in misfiring of cellular signalling pathways. Often, a metabolic reprogramming arising from these mutations in metabolic enzymes leads to the overproduction of so called ’oncometabolites’ in a state of ‘pseudohypoxia’. This can inactivate several of the intracellular molecules involved in epigenetic and redox regulations, thereby increasing oxidative stress giving rise to growth advantages for cancerous cells. Undeniably, these are cell-type and Reactive Oxygen Species (ROS) specific, which is manifested as changes in the enzyme activation, differences in gene expression, cellular functions as well as cell death mechanisms. Photodynamic therapy (PDT) using light-activated photosensitizing molecules that can regulate cellular redox balance in accordance with the changes in endogenous ROS production is a solution for many of these challenges in cancer therapy.

The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension

“…Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS), and reactive nitrogen species and the antioxidant defense systems [ 55 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. ROS are produced by cell organelles, including the mitochondria, peroxisomes, and endoplasmic reticulum, and consist of free radicals and non-radical derivatives.…”

“…Free radicals are a class of oxygen atoms that contain unpaired electrons that include superoxide (O 2 − ), hydroxyl radical (OH − ), lipid peroxyl-radicals (LOO − ), and alkoxy-radicals (LO − ). Non-radicals include H 2 O 2 , peroxynitrite (ONOO − ), hypochlorous acid (HOCl − ), lipid hydroperoxide (LOOH), ozone (O 3 ), singlet oxygen ( 1 O 2 ), and reactive carbonyls [ 55 , 59 , 60 , 61 , 62 ]. ROS are naturally generated from various bodily reactions, such as the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, cyclooxygenases, xanthine oxidases, lipogenesis, iron-catalyzed Fenton reaction, and nitric oxide synthases (NOS) [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

“…Non-radicals include H 2 O 2 , peroxynitrite (ONOO − ), hypochlorous acid (HOCl − ), lipid hydroperoxide (LOOH), ozone (O 3 ), singlet oxygen ( 1 O 2 ), and reactive carbonyls [ 55 , 59 , 60 , 61 , 62 ]. ROS are naturally generated from various bodily reactions, such as the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, cyclooxygenases, xanthine oxidases, lipogenesis, iron-catalyzed Fenton reaction, and nitric oxide synthases (NOS) [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. A major site for the intracellular production of ROS is from the process of mitochondrial respiration that occurs in all cells, including vascular and renal mesangial and tubular cells [ 55 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ].…”

“…In the rat kidney, NADPH oxidase accounts for about half of ROS production, with the remaining half from mitochondria [ 69 ]. Normal generation of ROS is important in cellular signal transduction [ 59 , 60 , 61 , 62 , 63 , 70 ]. Levels of ROS are decreased by endogenous and exogenous antioxidants.…”

“…Levels of ROS are decreased by endogenous and exogenous antioxidants. Endogenously generated antioxidants include enzymatic and non-enzymatic antioxidants, which consist of metabolic and nutrient forms [ 59 , 60 , 61 , 62 ] ( Table 1 ).…”