(close window)

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.

Oxidative stress inducers represent a novel approach to treating cancer. They are distinct from chemotherapy, from "targeted" agents such as kinase inhibitors and antibodies, and from angiogenisis inhibitors in that OS inducers exploit a fundamentally different vulnerability of cancer cells - their elevated levels of reactive oxygen species.

(close window)