Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer.
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.
1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, TX 77030, USA [2] Institute Science Biology, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia [3] Center for Research in Biotechnology for Agriculture, University of Malaya, Kuala Lumpur 50603, Malaysia.
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Hasima
1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, TX 77030, USA [2] Center for RNA Interference and Non-Coding RNAs - Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, TX, USA.
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Ozpolat
D000098:Acetophenones / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D000071186:Beclin-1; D001578:Benzopyrans / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003474:Curcumin / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D019833:Genistein / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059808:Polyphenols / Q000627:therapeutic use*; D011794:Quercetin / Q000627:therapeutic use; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000627:therapeutic use
D000098:Acetophenones; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D001578:Benzopyrans; D008565:Membrane Proteins; D059808:Polyphenols; D013267:Stilbenes; D011794:Quercetin; D019833:Genistein; C085746:rottlerin; D003474:Curcumin; D000077185:Resveratrol