Abstract
Cancer is one of the most serious diseases endangering human health. In view of the side effects caused by chemotherapy and radiotherapy, it is necessary to develop low-toxic anti-cancer compounds. Polyphenols are natural compounds with anti-cancer properties and their application is a considerable choice. Pro-senescence therapy is a recently proposed anti-cancer strategy and has been shown to effectively inhibit cancer. It is of great significance to clarify the mechanisms of polyphenols on tumor suppression by inducing senescence. In this review, we delineated the characteristics of senescent cells, and summarized the mechanisms of polyphenols targeting tumor microenvironment and inducing cancer cell senescence for cancer prevention and therapy. Although many studies have shown that polyphenols effectively inhibit cancer by targeting senescence, it warrants further investigation in preclinical and clinical studies.
Highlights
Cancer, a disease with a high incidence and mortality, has become one of the most significant health problems
CXCR2: C-X-C motif chemokine receptor 2; DDR: DNA damage response; ROS: reactive oxygen species; DLC1: deleted in liver cancer1; SASP: senescence-associated secretory phenotype; Pokemon: POK erythroid myeloid ontogenic factor; SIRT1: silent information regulator 1; Rictor: rapamycin-insensitive companion of mammalian target of rapamycin; hTERT: human telomerase reverse transcriptase; Rb: retinoblastoma protein; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; PI3K: phosphoinositide 3-kinase; AKT: protein kinase B; DEPP: decidual protein induced by progesterone; HER-2/neu: human epidermal growth factor receptor 2; RNS: reactive nitrogen species; Endoplasmic Reticulum (ER) stress: endoplasmic reticulum stress; ATF4: activating transcription factor 4; DDIT3: DNA damage inducible transcript 3; TRIB3: tribbles pseudokinase 3; mTOR: mammalian target of rapamycin; UPR: unfolded protein response; AMPK: AMP-activated protein kinase
We demonstrated that resveratrol increased expression of silent information regulator 1 (SIRT1) to reduce SASP and inhibited age-dependent spontaneous tumorigenesis in annual fish Nothobranchius guentheri [90,91]
Summary
A disease with a high incidence and mortality, has become one of the most significant health problems. The anti-tumor profile of polyphenols puts them in the spotlight of research fields Polyphenols exert their potential in anti-cancer therapy via promoting apoptosis, regulating autophagy, inhibiting proliferation and migration, and so on. Polyphenols extracted from Annurca apple selectively inhibited the viability of MDA-MB-231, a triple negative human breast carcinoma cell line, by causing G2/M phase arrest, inducing intrinsic and extrinsic apoptosis and beclin-1-independent autophagy [13]. A total of 20 genes were upregulated in senescent cells, and six of them were upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence [28] These results indicate that senescence induction requires lower drug concentrations compared to induction of apoptosis, which means that pro-senescence therapy has fewer side effects in terms of drug toxicity. We described cell senescence and focused on polyphenols and on their anti-cancer effects and molecular mechanisms for cellular senescence
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