Using Nutrigenomics to Evaluate Apoptosis as a Preemptive Target in Cancer Prevention

Keith R. Martin

doi:10.2174/156800907781386650

Abstract

Apoptosis, a form of programmed cell death, is a pivotal defense against cancer and is essential in maintaining tissue homeostasis. Many diseases including cancer have been associated with aberrantly regulated apoptotic cell death, thus elucidation of events associated with both apoptosis and carcinogenesis provides the opportunity for dietary intervention with the plethora of bioactive components in the diet. Apoptosis occurs primarily through two well-recognized pathways in cells including the intrinsic, mitochondrialmediated pathway and the extrinsic, death receptor-mediated pathway. Dietary components can modulate apoptosis through effects on protein expression and function, mRNA expression, and on the human genome, either directly or indirectly, to modulate gene expression. Thus, apoptosis is an emerging target of dietary bioactive agents. However, apoptosis is a complex process, with numerous specific targets within each pathway that may or may not overlap. Furthermore, biological systems are also extremely complex and exhibit properties that extend far beyond observations associated with each independent cellular process. This is further complicated by the temporal nature of many of these effects. As a result, it is critical to evaluate the entire biological system from the nutrigenomics perspective to include critical evaluation of DNA polymorphisms or SNPs of a gene, expression of that specific gene, expression of specific processed mRNA (alternative splicing), protein production from that mRNA, post-translational modification of the resultant protein, and formation of respective metabolites. Evolution of the fields of nutrigenetics, epigenomics, transcriptomics, proteomics, and metabolomics has begun to permit this approach so that a comprehensive picture emerges from not only a single cell but tissues and whole organisms. Studies such as these can ultimately be used to study tumors to understand the molecular events that accompany carcinogenesis and perturbations that occur during cell death processes and how an individuals response to diet can impact these processes.

Keywords: Apoptosis, nutrigenetics, epigenomics, transcriptomics, metabolomics, proteomoics, bioactive agent, DNA methylation, histone