Oxidative Stress in Prostate Cancer

Changing Research Concepts Towards a Novel Paradigm for Prevention and Therapeutics

A Paschos; R Pandya; W C M Duivenvoorden; J H Pinthus

Disclosures

Prostate Cancer Prostatic Dis. 2013;16(3):217-225. 

In This Article

Redox Homeostasis: ROS Production and Elimination

Reactive oxygen species (ROS), also termed oxidants, are common by-products of the standard aerobic cellular metabolism, continuously formed in the cell and synchronously scavenged by an array of antioxidant mechanisms.[1] Oxidative stress occurs following an increase in the ROS production and/or a simultaneous impairment of the antioxidative capacity of a cell.[1] Although ROS are often considered as a single entity, the term encompasses a wide and different range of oxidants (ROS physiome) encountered in biological systems, such as superoxide (O2), hydrogen peroxide (H2O2), hydroxyl (OH), nitric oxide (NO), peroxynitrite (ONOO), hypochlorous acid (HOCl), alkoxyl (RO), nitrogen dioxide (NO2), alkyl peroxyl (ROO) and many others.[2] In prostate cancer (PC), the most abundantly reported ROS are likely O2− contained as H2O2,[3] and presumably OH, NO and OONO. ROS interconvert with reactive nitrogen species (for example, NO, ONOO, NO2), which exert similar effects as ROS and, when in excess, are known to cause nitrosative stress.[4]

Both exogenous and endogenous sources contribute to the formation of intracellular ROS.[1,2] Exogenous sources include radiation and environmental agents. Major endogenous sources of cellular ROS are the microsomes, peroxisomes and mitochondria. ROS production in the mitochondria is the best studied, where it is coupled to the oxidative phosphorylation process. At the molecular level, ROS production takes place continuously at redox-active centers within enzymes or when ubiquinone (coenzyme Q10 (CoQ)), the essential electron carrier, accepts or donates electrons. Unique bioenergetic conditions are required to occur, such as high NADH-H+/NAD ratio or a high proton-motive force across the inner mitochondrial membrane (Δp) and concomitantly reduced CoQ pool (CoQH2), to accelerate ROS formation in the mitochondria.[5] Immune cells, such as granulocytes and macrophages, possess oxygen-dependent cytoplasmic mechanisms to form ROS following ingestion of a bacterium (phagocytic nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, myeloperoxidase). Other endogenous sources of ROS include enzymes such as xanthine oxidase, amino-acid oxidases, lipoxygenase and cyclooxygenase. Superoxide release as a result of the activity of the latter two enzymes may be especially important in PC because of prostaglandin biosynthesis.[6] Finally, membrane-associated NADPH-oxidases (ROS-generating NOX family)[7] emerged in recent years as the most considerable source of ROS in many malignancies, including PC.[3,8]

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