A lesson in the study of 'phytochemicals' in anti-cancer research

Better Nutrition, March, 1997 by Daniel Mowrey

For good or for bad, we are entering a new age in medicinal plant research. More and more, we see greater usage of the new buzz word "phytochemicals." This involves looking for benefits in isolated specific chemicals within plants instead of in whole plants, and parallels the shift from sole reliance on whole vegetables and fruits and other foods toward supplementation with vitamins and minerals.

Talk of such phytochemicals as procyanidins, flavonoids, antioxidants, carotene, etc., has replaced discussion of vitamin A and zinc. But we still want it all in a little capsule-size package. This new movement may be just a natural progression in nutritional evolution. At the very least, proper implementation of new research findings will demand a great degree of sophistication on the part of herb manufacturers and interest on the part of the consumer.

Making practical sense of the science of phytochemistry

Of course, research on individual plant chemicals is not new; it is just that we are feeling a greater need to make practical sense of it. Typically, such research is dense and requires an extensive education in biochemistry, physiology, pharmacology, medicine, and biophysics to understand it. To make the study more approachable, we look for biomedical models that can be used to show the benefits of individual medicinal agents. One such model is experimentally-induced skin cancer. Let's use this as an example of how we might go about the process of understanding the science of phytochemistry.

The sequential steps in the formation of skin cancer include the initiation of the tumor, the promotion or propagation of the tumor, and the progression of the tumor. Typically, the mutational events of tumor initiation are irreversible, so one basic approach to skin tumor prevention is to identify naturally-occurring substances that can inhibit the reversible propagation stage. We start by obtaining a substance, say TPA (12-0-tetradecanoylphorbal 13 acetate), that is known to cause changes in the skin that lead to tumor propagation, changes like initiation of activity of ODC (ornithine decarboxylase), stimulation of Hpx (hydroperoxide) production, and an increase in DNA production.

Next, researchers identify plant substances that they suspect block those events induced by TPA. Frequently, selected materials are polyphenolic materials, notably tannins. which are widely distributed in the plant kingdom: gallotannins, ellagitannins, proanthocyanidins, or procyanidins.

Ellagic acid and gallotannins decrease mutation, tumor initiation, and complete carcinogenesis, and, not surprisingly, prevent the biochemical events of TPA, therefore showing strong antitumor-promoting activities in the experimental model as applied to the skin in living mice (the TPA model is painless and harmless and is, therefore, a suitable model for living organisms).

Procyanidins from green tea have anti-cancer abilities

Likewise, procyanidins extracted from green tea possess anti-mutagenic and anticarcinogenic activity, and inhibit tumor initiation and promotion in the skin and other organs. Oligomeric tannins from loblolly pine, and several flavonoids (catechins and epicatechins) also significantly block the effects of TPA application to mouse skin.

As research progresses, all kinds of seemingly insignificant details are discovered, but which may ultimately prove to be of inestimable value in assessing the benefits of various plant materials.

Another finding to emerge from this line of research is that the anti-cancer action of tannins is paralleled by their antioxidative activity.

It is suggested that these substances interfere with molecular pathways regulating enzyme activities; they have a high reducing (opposite of oxidizing) power and form complexes with some metal ions and cofactors that are required in the generation of free radicals that cause the cancer. Or they may act simply by increasing the nonspecific immune response of the body, or both.

As data like these continue to accumulate about the mechanisms of action of all the classes of phytochemicals, it will provide more, and more, of the science base from which we can make our dietary-supplementation decisions.