Apoptosis by dietary agents for prevention and treatment of cancer

Abstract

The role of apoptosis or programmed cell death in the regulation of development and maintenance of homeostasis in multicellular organisms is well established. During the last decade, naturally occurring dietary agents known to produce chemopreventive effects in experimental models have been shown to target signaling intermediates in apoptosis-inducing pathways. Apoptosis is triggered by two different signals, one extrinsic, which responds mainly to extracellular stimuli, and the other intrinsic, activated by modulators within the cell itself. Proapoptotic compounds could protect against cancer by enhancing elimination of initiated, precancerous cells, and antiapoptotic compounds could promote tumor formation by inhibiting apoptosis in genetically damaged cells. In this brief review, we explore the potential mechanistic interactions of various dietary cancer chemopreventive components within the context of apoptosis.

FIG. 1

Dietary agents known to induce apoptosis by interfering with the extrinsic and the intrinsic apoptotic pathways. In the extrinsic pathway, a specific ligand binds to its corresponding cell surface death receptor and promote the recruitment of adapter molecule FADD to activate caspase-8 which trigger the activation of downstream effector caspases such as caspase-3, thereby propagating apoptosis. The intrinsic pathway of apoptosis relies on the permeabilization of mitochondrial membrane to release the apoptogenic mitochondrial proteins which translocate to mitochondria where they induce the release of cytochrome c either directly or through complexes with membrane proteins. Cytochrome c together with Apaf-1 and procaspase-9 forms apoptosome where activation of caspase-9 occurs. The two pathways of apoptosis merge as caspase-9 is capable of either directly or indirectly activating caspase-8 which mediates the proteolytic activation of BID. EGCG, resveratrol, curcumin, genistein, luteolin, lupeol, and indole-3-carbinol target the death receptor pathway whereas EGCG, resveratrol, apigenin, fisetin, pomegranate, delphinidin, lupeol, curcumin, genistein, luteolin, indole-3-carbinol, capsaicin and silibinin target the mitochondrial pathway of apoptosis.