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A radical moment with Dr. DNA

On an opportune meeting

Lori Bystrom 9 March 2013

www.lablit.com/article/765

Vitamins: not always the good guys?

I do not see anti-oxidants as the superstars that many beverage and food companies make them out to be

During the beginning of my career as a graduate student I became interested in antioxidants, especially those that came from natural foods. I was intrigued by the ability of antioxidants to quench or alter damaging chemicals into less-toxic compounds, and thereby potentially to prevent disease. I researched every kind of antioxidant assay that was available and tried many of them on different types of plant extracts. I especially recall one summer I spent in the Caribbean screening an array of tropical plants of various colors, shapes, sizes and parts (fruits, leaves, roots, etc.) for antioxidant activity. Much to my amazement, I found that everything I had tested had antioxidant activity, except one root extract, which in retrospect was probably my most interesting discovery.

After a year of this kind of research I came to the conclusion that 1) nearly everything has antioxidants, 2) there are no standardized tests to evaluate antioxidants (albeit some are more common than others), which is especially problematic when different assays yield inconsistent results, and 3) there is no meaningful health information that can be obtained from antioxidant assays of plant extracts. My disillusion with the world of antioxidants eventually led to a dissertation that focused more on chemical structure elucidation and biological assays, and less so on antioxidants.

Now several years later as a postdoctoral researcher, I find myself dabbling in the world of antioxidants again. However, this time I view antioxidants differently; I do not see them as the superstars that many beverage and food companies make them out to be. In fact, my current research focuses on the opposite of antioxidants and what many people consider their arch-rival to good health —prooxidants or free radicals, also known as reactive oxygen species (ROS), which are often associated with causing cancer and other disease states. However, these so-called evil pro-oxidants are actually what more and more researchers are finding to be the "good guys" that selectively target cancer cells.

Due to the high oxidative stress in the tumor cell environment (high ROS), cancer cells are more vulnerable to the toxic effects of pro-oxidants compared to their normal cell counterparts. In other words, it has been found that some prooxidants can target cancer cells without damaging healthy cells. A paper published by Raj et al. in Nature in 2011 demonstrated some of these effects by a natural compound known as piperlongumine (1). Of course, it is much more complicated than just taking a pill of prooxidants to cure cancer. It is still unclear what types of prooxidants work best, and how exactly they work in cancer cells. Nonetheless, it has made some researchers begin to reconsider the benefits of antioxidants that eliminate or quench prooxidants, especially for people who already have cancer. In fact, some research has shown that antioxidants can actually help cancer cells survive (2).

This brings me to my meeting with Dr. James Watson, who many of you may recall is one of the co-discoverers of the structure of DNA and co-recipient of the Nobel prize in physiology or medicine in 1962.

I had just published a review about cancer, iron and prooxidants when someone informed me that Dr. Watson had also recently published a review that similarly discussed the benefits of prooxidants in cancer research. I quickly found his publication in Open Biology and discovered a very interesting paper outlining his thoughts on the most promising approaches for cancer research (3). As fortune will have it, I discovered he was to give an in-house seminar at Cold Spring Harbor Laboratory the following week. I quickly re-arranged my schedule and made the trek out to Long Island to attend his seminar.

The eighty-something year old Dr. Watson made his appearance at the podium and started off with a long prologue about how he became interested in cancer research. He made funny, off-the-wall and slightly inappropriate comments here and there and I found him to be quite the character. However, age had not tarnished his intellect. After a brief introduction to oxidative stress and antioxidants he said something that I will not forget: "Scientists focus too much on DNA and not the chemistry". I couldn't agree more. Here was Dr. DNA himself telling people to focus more on chemistry. I admit I am partial to his statement because I always harbored more love for chemistry than for genetics, but it seemed to make sense. However, I should point out that Dr. Watson himself is not a chemist. Therefore, when I raised my hand to ask him what his thoughts were on a specific class of chemicals that induce oxidative stress, he merely stated a chemist would have to answer that question.

Although Dr. Watson pointed out that the consumption of antioxidants may not be the best for late-stage cancer patients, he only referenced studies focused on two antioxidants (vitamin C and E). He also made some references to orange juice as a source of antioxidants and implied it may function similarly as vitamin C. However, he did not talk about the complex mixture of plants and their many different types of antioxidants that may also function as prooxidants in different environments, such as in cancer cells (4). Moreover, it should be noted that eating a combination of plant chemicals of variable chemical structures is not the same as consuming individual antioxidants like vitamin C and E. Clearly more work needs to be done in this area to help scientists and clinicians understand the effects of natural foods/supplements, especially those reported to have high amounts of antioxidants.

After Dr. Watson's seminar I couldn't help but walk up to him and introduce myself and my research. He nodded and asked where I did my work. He seemed vaguely interested for a moment – or perhaps he was thinking about his book Avoid Boring People. I may never know. Regardless, I thoroughly enjoyed his seminar and I have to say I was pleased that he was promoting an area of cancer research that has been somewhat neglected— chemistry. Moreover, it is good to know that someone significant in the scientific world is finally encouraging people to take a more critical, if not radical, look at antioxidants.

References:

1. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X, et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature. 2011;475(7355):231-234.

2. Albright CD, Salganik RI, Van Dyke T. Dietary depletion of vitamin E and vitamin A inhibits mammary tumor growth and metastasis in transgenic mice. J Nutr. 2004;134(5):1139-1144

3. Watson J. Oxidants, antioxidants and the current incurability of metastatic cancers. Open Biol. 2013;3(1):120144; doi: 10.1098/rsob.120144.

4. Babich H, Schuck AG, Weisburg JH, Zuckerbraun HL. Research strategies in the study of the pro-oxidant nature of polyphenol nutraceuticals. J Toxicol. 2011; doi:10.1155/2011/467305.

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