Abstract
Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular stressors such as nutrient or growth factor deprivation, it can also lead to a non-apoptotic form of programmed cell death (PCD) called autophagy-induced cell death or autophagy-associated cell death (type II PCD). Current evidence suggests that cell death through autophagy can be induced as an alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells that are resistant to apoptosis. Thus, modulating autophagy is of great interest in cancer research and therapy. Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol, can trigger type II PCD via various mechanisms through the canonical (Beclin-1 dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The capacity of these compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. This review focuses on the autophagy- and cell death-inducing effects of these polyphenolic compounds in cancer.
Highlights
Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol can alter the effects of signaling pathways and induce cell death via apoptosis and via autophagy
Rottlerin or its related analogs may be used in the development of novel agents for the induction of autophagic cell death as it has been proven, pharmacodynamically in a mice xenograft model, to be efficiently absorbed in cells and tissues against pancreatic cancer
In this review, which is an update to previous reports by our group,[3,12,13] we look into the effects of five common dietary polyphenols – rottlerin, genistein, quercetin, curcumin, and resveratrol – on autophagy in several cancer types and their
Summary
The induction of cellular senescence was accompanied by autophagy in colon cancer cells with an increase in Beclin-1 and p62/SQSTM1 protein levels. The ability of natural polyphenolic compounds to induce autophagic cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. Natural plant-derived polyphenols are chemical substances characterized by the presence of more than one phenol unit per molecule They are present in some foods and have been shown to exert anticancer properties. Some important examples are rottlerin, genistein, quercetin, curcumin, and resveratrol, all of which have been shown to induce autophagy death in various cancer cells (Figures 1, 2, 3 and Table 1). In this review, which is an update to previous reports by our group,[3,12,13] we look into the effects of five common dietary polyphenols – rottlerin, genistein, quercetin, curcumin, and resveratrol – on autophagy in several cancer types and their
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