Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents

Abstract

Nontoxic naturally occurring compounds, especially those from dietary sources, are receiving increasing consideration for prevention and treatment of diseases including cancer. There is a growing need for innovative anticancer therapies and therefore search for natural compounds with novel biological activities or antineoplastic potential is currently an important area in drug discovery. Support for this interest also comes from increasing concern over the efficacy and safety of many conventional therapies, especially those that run over a long course of time. Laboratory studies in different in vitro and in vivo systems have shown that many natural compounds possess the capacity to regulate response to oxidative stress and DNA damage, suppress angiogenesis, inhibit cell proliferation and induce autophagy and apoptosis. This review discusses the induction of apoptosis and autophagy as a mechanism of cancer prevention by some of the most studied naturally occurring dietary compounds.

Figure 1

Effects of dietary compounds on extrinsic and intrinsic pathways of apoptosis. The extrinsic pathway is triggered by death receptors and involves activation of the initiator caspase-8, which directly activates caspase-3 causing apoptosis. The intrinsic pathway is activated by different apoptotic stimuli that lead to release of cytochrome c from mitochondria and activation of caspase-9. The endoplasmic reticulum is triggered by stress and stimulates mitochondria to release cytochrome c and cause DNA damage. Many dietary agents affect molecules at several steps to initiate removal of unwanted cells by inducing apoptosis. EGCG is known to affect both the intrinsic as well as the extrinsic pathways and induces apoptosis in many cancer types.