Nobel-winner Watson: Do antioxidants promote cancer?

Antioxidant foods and pills could heighten the risk of cancer and diabetes, argues the co-discoverer of the structure of DNA

ANTIOXIDANTS have long been touted as powerful disease-preventing agents. Billions of dollars are spent annually on antioxidant supplement pills. Untold additional sums are spent by health-conscious consumers loading up on antioxidant-rich foods like blueberries and blackberries. However, claims that these products let human beings live healthier and longer lives do not stand up to serious scrutiny.

Many, many clinical trials reveal that they lead to virtually no improvement in the functioning of our cardiovascular systems. There is less data about antioxidants and cancer but the most recent large-scale trial to see whether the antioxidant vitamin E prevents cancer was halted when not only was no benefit shown, but slightly more prostate cancer was observed in vitamin E takers.

It is easy to see how antioxidants came to be regarded as an aid to health. The oxidising molecules, or oxidants, that they neutralise in our bodies, though essential to normal biological function, are toxic in excess. They damage DNA and proteins, and so can cause cancer. But this simplistic view overlooks overlooks evidence that a more complex system is at play (Open Biology, doi.org/kpp). For example, vegetables such as Brussels sprouts and broccoli that have been linked with anti-cancer benefits may actually generate these benefits through their ability to promote pro-oxidative cellular processes rather than antioxidative ones.

The fact that antioxidant dietary supplementation might lead to more not less cancer should come as no surprise to the world's better-informed cancer therapists, who know that ionising radiation treatment kills cancer cells largely through creation of oxidants called reactive oxygen species (ROS). And though it was generally believed that major chemotherapy drugs like paclitaxel kill each cancer through different means, there now is a growing consensus that they too are highly effective generators of the powerful oxidant superoxide, the hydrogen radical and hydrogen peroxide, the three major components of ROS.

This at last explains the long-disturbing findings that when a cancer becomes resistant to one form of chemotherapy, it simultaneously becomes resistant to all the other, better chemotherapy agents, as well as to further radiation therapies.

Recent research on pancreatic cancer has demonstrated that in cells of aggressive, resource-hungry tumours, antioxidant levels are greatly elevated. These endogenous antioxidants – synthesised by the body – arise to keep ROS from triggering sensors that initiate a process called apoptosis, or programmed cell death. This raises an important possibility: if we can learn how to reduce antioxidant levels specifically in cancer cells, we may be able to successfully treat many types of late-stage cancers that are now incurable.

To understand how we might achieve this goal, we first need to understand better how the body controls antioxidant levels. In the absence of ROS, levels of cellular antioxidants are normally kept to very low levels by an enzyme called Keap 1 ubiquitin ligase. This destroys a transcription factor – a molecule that controls gene expression – called Nrf2 that is used to turn on synthesis of the major antioxidants. When, however, ROS levels rise to therapeutically effective levels, Nrf2 transcription factors somehow become liberated and direct the synthesis of some 10 different antioxidants that destroy ROS.

I suspect that once a cell is committed to moving through the cell cycle to replicate, it turns up antioxidant synthesis to protect the vulnerable single-stranded chains of replicating DNA. Though most cancer therapists have long suspected that cells undergoing division are most vulnerable to cell-killing agents, the truth may be just the opposite. The recent important observation that populations of stem cells have relatively high antioxidant levels may be due in part to their higher content of cells undergoing cell division...

http://www.newscientist.com/article/mg21729080.200-nobelwinner-watson-do-antioxidants-promote-cancer.html?full=true