A New Wrinkle on an Old Remedy

For many years, naturopaths and health-conscious individuals have recommended the consumption of grape seed extracts. Chemical analyses of grape seeds have provided a treasure trove of active ingredients including resveratrol, anthocyanins, pro-anthocyanins, and numerous terpenes. Many of these substances are potent antioxidants and there is reason to believe that they may have meaningful health benefits.

As one of the editors of the Journal of Medicinal Food, I was asked to review an article on the chemical activities of grape seed extracts. I then wrote an editorial describing the interesting findings in this study and their biological relevance. The most interesting aspect of this well-conducted analysis was the description of a wholly new mechanism of action for the substances found in grape seeds. What the authors found was that the chemical species in grape seed extracts influence gene expression through a process knows as histone acetylation. What makes this so interesting is the fact the histone acetylation is one of the fundamental regulators of genetic expression and a critical part of the new field of science known as epigenetics.

Epigenetics is the field of study that examines heritable attributes that are not incorporated into DNA sequence. These epi-phenomena take existing genes and determine whether or not they will actually be expressed. The reason that this is so important is that it shines a very bright light on the limitations of genomic analyses (studies that examine the DNA sequence in tissues). Clearly, if the consumption of foodstuffs (like grape seed) can alter gene expression then the use of genomic profiles to predict cellular behavior can only be viewed as highly simplistic.

We are continually impressed by the complexity of biology and are humbled when we consider the intersecting pathways that take us from gene to function.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

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