do we study tocopherols, when we know Vitamin E is not limited to tocopherols?’ Back then almost all the research was on tocopher- ols, and less than 1% on tocotrie- nols. Lester said, “Well, if you’re interested, let’s research tocot- rienols.” But when I looked for tocotrienols, there was nothing available in the market. No won- der nobody had studied them! Finally I found a large company in Germany that held the patent on chemical synthesis of tocot- rienols, and we managed to get all eight forms of Vi- tamin E to study. We ordered them blind- ed, just coded in letter format, A, B, C, D, E, F, G, H. And we start- ed testing them in vi- tro using an established model of neurodegeneration.


Focus: And what you found caught your full attention, and start- ed you on your lifelong journey.


Sen: We were astonished to find that Sample C was significant- ly more effective in preventing neurodegeneration in cells in vi- tro than any other molecule. We published that paper in the year 2000 in the Journal of Biological Chemistry.1


I was the first author,


Lester the last author. At first, we thought perhaps Sample C was alpha-tocopherol. But no, it was alpha-tocotrienol. We then wanted to confirm our results, and when we compared the mol- ecules again, we found the differ- ence was not one or two fold, but a hundred fold, in terms of con- centration. It was not something you could ever miss. It was a really powerful result. But, be- ing scientists, we were still ter- ribly skeptical at the time, so we made the observation by saying


Sen: We found a pathway known


as cSrc (cellular-src,


In 2000 we tested all eight Vitamin E fractions on neuronal cells, and found that alpha-tocotrienol protected cells from degeneration at concentrations a thousand- fold less than any other form of Vitamin E.


we had to report this, but we had done no supportive work in vivo yet. When you are publish- ing groundbreaking research it is not enough to say you found a molecule was protective. You must also identify the path- way


or pathways which it protects.


Focus: So finding the path- way by which alpha tocotrienol works was your next step. What pathway(s) did you discover?


Dr Chandan Sen is currently the Associate Dean for Translational & Applied Research at The Ohio State University Wexner Medical Center. Dr. Sen is a widely recognized expert in redox and oxygen biology. He is the author of the most cited original work published


10 Focus April 2013 through


where src is short for sarcoma) as one powerful candidate. To put that in context, scientist Harold Varmus PhD, the previous di- rector of the National Institutes of Health, jointly won the 1989 Nobel Prize in Physiology or Medicine with Michael Bishop for discovery of the cellular or- igin of retroviral oncogenes. In 1970, he identified the oncogene Src and demonstrated its signifi- cance in cancer. The discovery of Src family proteins has been instrumental to the modern understanding of cancer as a disease where normally healthy cellular signaling has gone awry. Src biology is a very hot topic in the field of cancer. However, it turns out the human brain naturally has a lot of cSrc, and nobody knew what it was doing there. We were report- ing for the first time that tocotrie- nols, perhaps by inhibiting cSrc activity in the neural cells, could prevent neurodegeneration.


That was the beginning and we were terribly excited but we were also very worried about whether we could really ‘hang our hat’ on


during the last decade on tocotrienols. He is the Editor-in-Chief of the #1 rated journal in redox biology Antioxidants & Redox Signaling (impact factor 8.456). Dr. Sen has published over 250 publications and is cited over 1600 times in the literature annually.


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