Targeting apoptosis with dietary bioactive agents

Apoptosis, a form of programmed cell death, is a pivotal defense against the occurrence of cancer and is essential to metazoans in maintaining tissue homeostasis. Apoptosis exhibits a distinctive phenotype and involves elimination of potentially deleterious cells. Many diseases have been associated with aberrantly regulated apoptotic cell death, ultimately leading to inhibition of apoptosis and propagation of diseases such as cancer. Elucidation of the critical events associated with carcinogenesis provides the opportunity for dietary intervention to prevent cancer development through induction of apoptosis, particularly by bioactive agents or functional foods. Diet is a significant environmental factor in the overall cancer process and can exacerbate or interfere with carcinogenesis. Apoptosis occurs primarily through two well-recognized pathways in cells, including the intrinsic, or mitochondrial-mediated, effector mechanism and the extrinsic, or death receptor-mediated, effector mechanism. In addition to diet's effects on protein expression and function, evidence is also accumulating that a large number of dietary food components can exert effects on the human genome, either directly or indirectly, to modulate gene expression. In fact, many diet-related genes are involved in carcinogenesis as well as apoptosis, and thus are ultimately molecular targets for dietary chemoprevention. There are multiple steps within pathways in which dietary components can alter gene expression and phenotypes of cells and thus influence cancer outcomes (nutritional transcriptomic effect). Thus, apoptosis is an emerging therapeutic target of bioactive agents of diet. In this review, the process of apoptosis is discussed and the potential mechanistic interaction of bioactive agents, as components of functional foods, is explored within the context of apoptosis.