ROS in Cancer - What Are Reactive Oxygen Species?

ROS in Cancer: What are Reactive Oxygen Species?

Reactive Oxygen Species (ROS) is a phrase used to describe a number of reactive molecules and free radicals derived from molecular oxygen. These include singlet oxygen, superoxide radicals, peroxides, and hydroxyl radicals. The production of oxygen-based radicals is the bane of all aerobic species.

ROS is produced as a natural by-product of the normal metabolism of oxygen in the cells. However, during times of cellular stress (such as inflammation), ROS production can increase dramatically, leading to potential damage to cells.

While ROS are often thought of as being negative, they do have some positive roles in the body. For example, ROS can act as signaling molecules, helping to regulate various cellular processes. They can also help to kill bacteria and other pathogens.

However, too much ROS can lead to oxidative stress, which has been linked to a number of diseases, including cancer, heart disease, stroke, and Alzheimer’s disease.

Reactive Oxygen Species Examples:

• Singlet oxygen: One of the more well-known reactive oxygen species, singlet oxygen is highly reactive and can damage DNA, proteins, and lipids.
• Superoxide radicals: Superoxide radicals are produced when molecular oxygen loses an electron. These radicals can damage DNA, proteins, and lipids.
• Peroxides: Peroxides are another type of ROS that can damage DNA, proteins, and lipids.
• Hydroxyl radicals: Hydroxyl radicals are some of the most reactive and dangerous ROS. These radicals can damage all types of biomolecules, including DNA, proteins, carbohydrates, and lipids.

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 the initiation, progression, and metastasis of cancers, ROS are considered oncogenic.

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 -and 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, glutathione peroxidases (GPx 1–8), and peroxiredoxins (Prdx 1–6). SOD converts superoxide to H2O2 (and O2) while catalase, 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.

ROS in Cancer

The role of ROS in cancer is complex and depends on the type and stage of cancer. ROS can promote cancer by damaging DNA and other important molecules in cells. This damage can lead to mutations that allow cancer cells to grow and divide out of control. ROS can also help cancer cells to spread (metastasize) by damaging the extracellular matrix, a network of proteins and other molecules that helps to keep cells in place.

In addition, ROS can promote cancer by stimulating the growth of new blood vessels (angiogenesis), which cancer cells need to supply with oxygen and nutrients. However, ROS can also have negative effects on cancer cells. For example, ROS can damage cancer cell membranes and make them more susceptible to death. It is not clear why some cancers are more sensitive to ROS than others. In general, cancers with a high growth and division rate (such as leukemia) are more likely to be affected by ROS.

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 are the patient's chances.

Cytotoxic Lymphocytes

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, inhibiting 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.

Cu/Zn superoxide dismutase is a very efficient enzyme. A new cream-based treatment can simulate a Cu/Zn superoxide dismutase by delivering highly available zinc and copper directly through the skin. You can review its mode of action on this website.

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, which can predispose to cancer and age-related disorders.

We hope this will give you a better understanding of the role of ROS in cancer and how antioxidants can help prevent or treat this disease.