Two researchers have offered an explanation as to why antioxidants are not effective in fighting cancers and suggested a way to change that.
The duo proposed that antioxidants from supplements or dietary sources are proving ineffective because they are not acting where reactive oxygen species (ROS) are produced.
So therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, may be more effective.
David Tuveson, MD, PhD, of the Cold Spring Harbor Laboratory in New York, and Navdeep S. Chandel, PhD, of the Feinberg School of Medicine at Northwestern University in Chicago, detailed these theories in a report published in The New England Journal of Medicine.
The pair’s insights are based on recent advances in understanding the cell system that establishes a natural balance between oxidizing and antioxidizing compounds.
Oxidants like hydrogen peroxide are manufactured within cells and are essential in small quantities. But oxidants are toxic in large amounts, and cells naturally generate their own antioxidants to neutralize oxidants.
It has seemed logical, therefore, to boost a person’s intake of antioxidants to counter the effects of hydrogen peroxide and other similarly toxic ROS. All the more because cancer cells are known to generate higher levels of ROS to help feed their abnormal growth.
However, Drs Tuveson and Chandel proposed that taking antioxidant pills or eating foods rich in antioxidants may be failing to show a beneficial effect against cancer because antioxidants do not act where tumor-promoting ROS are produced—at mitochondria.
Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, “leaving tumor-promoting ROS relatively unperturbed.”
Therefore, the authors suggested therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, will be more effective than dietary antioxidants.
An alternative approach
Drs Tuveson and Chandel also proposed an alternative approach: disabling antioxidants in cancer cells. They noted that quantities of both ROS and natural antioxidants are higher in cancer cells. The higher levels of antioxidants are a natural defense by cancer cells to keep their higher levels of oxidants in check so that growth can continue.
In fact, therapies that raise the levels of oxidants in cells can be beneficial, whereas those that act as antioxidants may further stimulate the cancer cells.
So the authors suggested that genetic or pharmacologic inhibition of antioxidant proteins—a concept tested successfully in rodent models of lung and pancreatic cancers—may be a useful therapeutic approach in humans.
The key challenge is to identify antioxidant proteins and pathways in cells that are used only by cancer cells and not by healthy cells. Impeding antioxidant production in healthy cells will upset the delicate redox balance upon which normal cellular function depends.
So it seems research is needed to profile antioxidant pathways in tumor and adjacent normal cells, to identify possible therapeutic targets.
