Reactive Oxygen Species, Cellular Redox Homeostasis and Cancer

Abstract

Redox homeostasis is attained by the cautious regulation of both reactive oxygen species (ROS) formation and removal from the body system. A shift in ROS balance promotes oxidative injury and tumour development by inflicting damage to DNA and inducing inconsistencies in the genome. The sources of endogenous ROS in a cell include mETC, NOX, LOX, cytochrome P450 and XO. The exogenous risk factors of ROS are pollutants, chemicals/drugs, radiation and heavy metals. Oxidative phosphorylation in the mitochondria produces ROS with unpaired electrons. Superoxide anion is the major ROS produced in the human mitochondria. Bulk of the ROS generation in the mitochondria occurs at the electron transport chain as derivatives of respiration. Cancer cells sustain ROS production by suppressing the antioxidant-generation system. Balance between ROS production and subsequent detoxification is regulated by scavenging enzymes and antioxidant agents. Failure in sirtuin-3 (SIRT3), ATM and p53 activities elevates the intracellular levels of ROS. PKCα induces the expression of NOX (DUOX) during cancer development and the consequent increase in ROS production. The PI3K/AKT signalling pathway activates NOX with consequent ROS production and subsequent induction of instability in the genome, leading to cancer. In conclusion, the interruption of the redox pathways that regulate ROS and its redox signalling activities affects cell physiology and can ultimately result in abnormal signalling, uncontrolled oxidative impairment and tumorigenesis.

Mitochondrial Uncoupling Proteins (UCPs) as Key Modulators of ROS Homeostasis: A Crosstalk between Diabesity and Male Infertility?

“…They are a natural byproduct of the mitochondria’s oxidative phosphorylation, arising when a single unpaired electron reduces O 2 at the oxidative chain level, which results in formation of the superoxide anion. However, an unregulated increase in the production of these free oxygen radicals renders the cellular antioxidant system incapable of mitigating their harmful effects, causing a shift in the homeostasis of the redox balance towards oxidative stress, a damaging state that participates on the pathophysiology of several diseases and capable of inducing macromolecular damage towards apoptosis/necrosis [ 125 , 126 ]. It has been proposed that mild uncoupling of the mitochondrial oxidative phosphorylation system might prevent the oversupply of electrons to the various protein complexes of the electron transport chain, diminishing the possibility of electron leaks and interaction with oxygen.…”

Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis

“…Oxidants can play a dual role as both toxic and beneficial compounds, the latter due to their crucial role as essential signaling molecules (Pham-Huy et al, 2008). They are produced from both endogenous (e.g., cell metabolism) and exogenous (e.g., cigarette smoking, environmental toxins, chronic physiological stress, iron overload, inflammation, et cetera) sources and can contribute to disease via disruptions to cellular homeostasis by redox signaling (Bhattacharyya et al, 2014;Basria et al, 2019). Over time, exposure to multiple inciting factors, as well as the failure of enzymes responsible for redox homeostasis and detoxification activities, may trigger a chronic imbalance between ROS production and antioxidant defenses (Bhattacharyya et al, 2014;Basria et al, 2019).…”

“…They are produced from both endogenous (e.g., cell metabolism) and exogenous (e.g., cigarette smoking, environmental toxins, chronic physiological stress, iron overload, inflammation, et cetera) sources and can contribute to disease via disruptions to cellular homeostasis by redox signaling (Bhattacharyya et al, 2014;Basria et al, 2019). Over time, exposure to multiple inciting factors, as well as the failure of enzymes responsible for redox homeostasis and detoxification activities, may trigger a chronic imbalance between ROS production and antioxidant defenses (Bhattacharyya et al, 2014;Basria et al, 2019). Excess free radicals can lead to mitochondrial dysfunction by inducing mitochondrial DNA mutations, damage to its respiratory chain, alteration of its membrane permeability, and by influencing Ca 2+ homeostasis and mitochondrial defense systems (Guo et al, 2013).…”

Green cardamom mediated phytosynthesis of ZnONPs and validation of its antibacterial and anticancerous potential

“…Cellular abnormalities or even cell death is a normal consequence resulting from disruption of redox (reduction-oxidation) balance in a cancer cell [13]. Elevation in reactive oxygen species (ROS) level can be a major cause for promoting redox imbalancement leading to oxidative damage of the cell [14]. The lethal effect of ZnONPs to bacterial cells may result from the adherence of the mentioned nanoparticles to bacterial surface electrostatically in addition to the liberation of hydrogen peroxide due to the same agent [15].…”