Oxygen Based Radicals – Reactive Oxygen Species – Killer Cells – SOD

Reactive Oxygen Species (ROS) is a phrase used to describe a number of reactive molecules and free radicals derived from molecular oxygen.

The production of oxygen-based radicals is the bane to all aerobic species.

These molecules, produced as byproducts during the mitochondrial electron transport of aerobic respiration or by oxidoreductase enzymes and metal-catalyzed oxidation, have the potential to cause a number of deleterious events.

Reactive oxygen species such as superoxide (O2o) or its breakdown product hydrogen peroxide (H2O2) have been implicated in the development of several diseases such as diabetes, heart disease, mitochondrial disease, various neurodegenerative diseases, and cancer.

ROS play a major role in tumor initiation induced by a variety of agents both in animal models of disease and also in humans.

For example, ROS are implicated in tumor induction mediated by phorbol esters, organic peroxides, heavy metals, asbestos, cigarette smoke, and silica. In cancer cells, oxidative stress has been linked to the regulation of numerous cellular processes including DNA damage, proliferation, cellular adhesion and migration, and the regulation of cell survival or death.

Reactive oxygen species (ROS) act as a second messenger in cell signaling and are essential for various biological processes in normal cells. Any aberrance in redox balance may relate to human pathogenesis including cancers. Since ROS is usually increased in cancer cells due to oncogene activation, relative lack of blood supply, or other variances and ROS do involve in initiation, progression, and metastasis of cancers, ROS are considered oncogenic.

oxygen-based radicals

ROS production is a mechanism shared by all non-surgical therapeutic approaches for cancers, including chemotherapy, radiotherapy, and photodynamic therapy, due to their implication in triggering cell death, therefore ROS is also used to kill cancer cells. Because of the double-edged sword property of ROS in determining cell fate, both pro -or antioxidant therapies have been proposed for treatments of cancers.

Tissue damage caused by excessive production of oxidants is prevented by antioxidant enzymes. In mammals, the former class includes superoxide dismutases (SOD1 and SOD2), catalase, the glutathione peroxidases (GPx 1–8), and the peroxiredoxins (Prdx 1–6). SODs converts superoxide to H2O2 (and O2) while catalase, the glutathione peroxidases, and peroxiredoxins reduce H2O2 to H2O. GPxs and Prdx6 use glutathione as the reducing substrate, Prdxs 1–5 use reduced thioredoxin, and catalase dismutases H2O2 to H2O and O2. While all antioxidant enzymes have been linked to various aspects of cancer biology, SOD2 deserves special attention.

Redox regulation of the antitumor functions of natural killer cells, cytotoxic T lymphocytes, and lymphokine-activated killer cells.

Tumors that show a dense infiltration of immune cells are regarded as “hot” while tumors containing few immune cells are regarded as “cold”. In many cancers, the hotter the tumor the better is the patient´s chances

In the fight against cancer, cytotoxic lymphocytes (CLs) represent the most powerful soldiers in the army of the cellular immune system. The tumor redox environment affects the CL-mediated killing of cancer cells. Though cytotoxic lymphocytes are sensitive to excessive levels of oxidants that trigger inactivation and apoptosis, low levels of oxidants are needed for the lymphocytes to exert their cytotoxic functions.

H2O2 production by macrophages or myeloid cells has also been shown to fuel tumor progression via driving angiogenesis, promoting cancer cell proliferation, inhibition of mir328, and blocking differentiation of DCs and MΦs. Radiotherapy has also been shown to stimulate invasion and metastasis formation via oxidants (and H2O2-induced CXCR4 expression).

Tremendous efforts have been made to take advantage of intratumoral redox imbalance and turn it against cancer. The role of enzymatic (superoxide dismutase (Cu, Zn-SOD, Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin, and lipoic acid), flavonoids, selenium, and others) in the process of carcinogenesis.

Overproduced free radicals react with cell membrane fatty acids and proteins impairing their function permanently.

In addition, free radicals can lead to mutation and DNA damage that can be a predisposing factor for cancer and age-related disorders.

Redox control of cancer cell destruction
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842284/

Reactive oxygen species in tumor progression
https://www.bioscience.org/2005/v10/af/1667/fulltext.htm

Free radicals, metals, and antioxidants in oxidative stress-induced cancer.
https://www.sciencedirect.com/science/article/pii/S0009279705004333?via%3Dihub

Oxidative stress, inflammation, and cancer: How are they linked?
https://www.omicsonline.org/open-access/inflammation-free-radical-damage-oxidative-stress-and-cancer-ijm.1000109.php?aid=32604

An Introduction to Reactive Oxygen Species – Measurement of ROS in Cells
https://www.biotek.com/resources/white-papers/an-introduction-to-reactive-oxygen-species-measurement-of-ros-in-cells/

oxygen-based radicals

 

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