Salvestrols - Natural Anticancer Prodrugs in The Diet and A New Perspective in Nutritional Anticancer Research


H L Tan, P C Butler, M D Burke and G A Potter,


Traditional & Complementary Medicine Exhibition 2007 (TCME 2007)




Salvestrols, anticancer, cytochrome P450


The cytochrome P450 (or CYP) enzymes are widespread in nature and are present in all biological kingdoms. These enzymes catalyse the oxidative metabolism of a wide range of endogenous and exogenous compounds. A major focus of P450 research is on their ability to biotransform pharmaceutical drugs and to activate carcinogens. P450 might haveconferred an evolutionary advantage on humans by detoxifying noxious natural chemicals in their prehistoric diet. If so,then the reason why modern man-made chemicals, such as drugs and environmental pollutants, are metabolised by P450smay be their close resemblance to molecules in nature. Particular important among natural dietary substrates of humanP450s are the plant-based phytochemicals. A relatively new strategy for treating cancer is the design of prodrugs for specific activation by P450s that are highly overexpressed in cancer cells, such as CYP1B1 (1). In our laboratories this work led tothe discovery that the well-known dietary phytochemical, resveratrol, is metabolised by CYP1B1 in cancer cells to cytotoxicderivatives (2). Recently we have discovered several further natural dietary phytochemicals that are specifically activated into cytotoxic metabolites by CYPs overexpressed in cancer cells. These phytochemicals comprise diverse chemical types and have been given the collective name, Salvestrols. We suggest not only that Salvestrols exemplify a new mechanism of dietary anticancer action, but that the depletion of Salvestrols in the modern diet, as a result of modern agricultural andhorticultural practices, may be a major contributing factor to the increase of cancer incidence in human populations eventhough consumption of fruits and vegetables is increasing year by year.