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Oxidative Stress and Cancer

Oxidative stress in cells is the presence of elevated levels of reactive oxygen species (ROS) such as oxygen radicals and hydrogen peroxide. ROS can be generated by many processes and stimuli, including ordinary cell metabolism, exposure to heat or radiation, or attack by bacteria or viruses. Because ROS can react chemically with different proteins and other elements of a cell, altering their normal function, prolonged exposure to elevated levels of ROS can cause serious damage to a cell. To protect against this damage, cells have natural defense mechanisms – anti-oxidant abilities – to clear excessive levels of ROS and to repair the disruption they cause. These mechanisms include specialized agents that clear ROS, known as anti-oxidants, as well as specialized repair proteins, known as stress or chaperone proteins.

Normal, non-cancer cells typically function at a low, steady-state level of oxidative stress. Their strong anti-oxidant capacity guards against prolonged, excessive levels of ROS.

Cancer cells, however, typically operate at a much higher level of oxidative stress than normal cells, and have a greatly diminished anti-oxidant capacity. This diminished capacity to clear ROS leaves them vulnerable to further increases in oxidative stress. In particular, when ROS levels exceed a natural breaking point, continued survival of the cell becomes unsustainable. At levels of ROS above this breaking point, a switch inside the mitochondria is triggered that causes the cell to initiate programmed cell death, also known as apoptosis.

In other words, the diminished anti-oxidant capacity of cancer cells, relative to normal cells, leaves them vulnerable to an agent that increases ROS levels beyond the breaking point.

While this fundamental difference between normal cells and cancer cells has been known for many years, recently there has been a rapid increase in the number of scientific research and publications in the field.

Excerpts from Recent Publications:

“… increased ROS can be seen as the Achilles heel of cancer cell metabolism.” - Reactive Oxygen Species: A Breath of Life or Death? L. Fruehauf and F.L. Meyskens (2007) Clin. Cancer Res. 13:789-794.

“…further oxidative stress … could exhaust the cellular antioxidant capacity and push ROS levels beyond a “threshold”, leading to apoptosis.” - ROS Stress in Cancer Cells and Therapeutic Applications Pelicano et al. (2004) Drug Resistance Updates 7:97-110.

“… cancer cells normally produce more ROS than do normal cells… addition of an agent that increases ROS … may push a tumor cell beyond the breaking point …” - Reactive Oxygen Species in Cancer Cells: Live By The Sword, Die By The Sword P.T. Schumacker (2006) Cancer Cell 13:175-176.

The growing interest represents the potential of ROS-elevation as a novel anti-cancer strategy. Most widely used anti-cancer agents differentiate by one of three established means:

Oxidative stress induction represents an entirely novel way of selective tumor cell killing: exploiting the difference in oxidative stress levels and anti-oxidant capacity between normal cells and cancer cells.

While some cancer therapies – for example certain cytotoxic agents – can increase oxidative stress, this is not their primary mechanism of action and is believed to be a “downstream” effect of such drugs. To date, we are aware of no drugs that have been approved whose primary mechanism of action is based on induction of oxidative stress.

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