APOPTOSIS, CANCER, AND OVEREXPRESSION OF PROTEINS Cancer Prevention by Food Factors Through Targeting Signal Transduction Pathways

Chemoprevention may be defined as the use of non-toxic substances, including many food factors, to interfere with the process of cancer development or carcinogenesis before invasion and metastasis can occur. For these substances and food factors to be effective chemopreventive agents, they must have an impact on a “valid” cellular or molecular target. What determines a “valid” molecular or cellular target? Substantial progress has been made in the identification of molecular and cellular targets for the use of cancer preventive agents; and hundreds of food compounds have been identified as potential cancer preventive agents. However, very few of these food components have been shown to be effective in clinical trials; therefore, much more progress needs to be made in identifying “valid” targets for effective use of nutrient chemopreventive agents. Carcinogenesis is a multistage process in which numerous genes important in the regulation of cellular functions may be prime targets for cancer preventive agents. Food factors can influence genetic and epigenetic events associated with several cancer processes, including DNA repair, carcinogen metabolism, cell cycle regulation, DNA methylation, apoptosis, differentiation, and hormonal regulation. The validity of a food factor–targeted molecule will depend on cancer type and the individual response to the food factor. The response is further confounded by genetic variability. Thus a greater understanding of the molecular targets for nutrients is needed. Obviously, bioactive compounds have the potential to be beneficial in some circumstances and detrimental in others. In addition, the “effectiveness” of a dietary substance will depend on the absorbed dose. A major focus of our work has been to identify the targets of “natural” non-toxic chemopreventive compounds present in what we commonly eat or drink. These compounds have potent anticancer effects that work through unknown mechanisms. However, their effects are very likely related to their influence on “valid” molecular targets. We propose that, for a substance or food factor to be an effective chemopreventive agent, it must influence a “valid” molecular target and specific criteria must be met for a molecule to be a “valid” target for effective cancer prevention.