Polyphenolic Compounds Targeting p53-Family Tumor Suppressors: Current Progress and Challenges

Étienne-Selloum, Nelly; Dandache, Israa; Sharif, Tanveer; Auger, Cyril; Schini‐Kerth, Valérie B.

doi:10.5772/56102

Cited by 10 publications

(12 citation statements)

References 229 publications

(255 reference statements)

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“…Phosphorylation of p53 at ser15 occurred as a response to DNA damage that resulted from a single-or double-strand break (38). Previous research has shown that other polyphenols induce p53 expression by inducing DNA damage, which triggers the ATM/CHK kinases that cause phosphorylation to the p53 (35). Here, we found that EA induced phosphorylation of p53 at ser15 in 22RV1 cells, indicating a DNA damage mechanism induced by EA in 22RV1 cells.…”

Section: Discussionsupporting

confidence: 57%

MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro

Saleem

Selim

2020

Oncol Rep

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Prostate cancer (PCa) is the most common cancer in men. Despite the available treatments for PCa, a significant number of patients relapse as the disease becomes hormonal-independent. p53 is a common tumor suppressor; however, its activity is diminished via the overexpression of murine double minute-2 (MDM2). The pomegranate, walnuts, and blueberries are widely consumed fruits and nuts that contain several polyphenolic compounds, mainly ellagic acid (EA). The present study focused on the influence of EA on the p53/MDM2 pathway in PCa cell lines. Three human PCa cell lines PCa LNCaP (p53 +/+ ), 22RV1 (p53 −/+ ), and PC3 (p53 −/− ) harboring different p53 genotypes were used in this research. We found that EA downregulated the gene and protein expression levels of MDM2 and increased the protein expression of p53 as determined by qPCR and western blot analyses. Moreover, by using western blot analysis, we determined that EA increased the protein expression of the p53 target proteins p21, p53 upregulated modulator of apoptosis (PUMA) [also known as Bcl-2-binding component 3 (BBC3)] and Phorbol-12-myristate-13-acetate-induced protein 1 (NOXA). Furthermore, we found that EA induced apoptosis in the absence of p53 by downregulating MDM2 and X-linked inhibitor of apoptosis protein (XIAP) protein expressions as determined by western blot analysis. We conclude that EA suppressed PCa cells in vitro partly by downregulating MDM2.

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Section: Discussionsupporting

confidence: 57%

MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro

Saleem

Selim

2020

Oncol Rep

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“…It has to be pointed out that the tumor suppressor p53 is a transcription factor that regulates a broad range of processes among which cell cycle arrest, senescence, and apoptosis are the best characterized. In vitro and in vivo studies have shown that polyphenols such as, epigallocatechin, resveratrol, and curcumin as well as nutritional sources of polyphenols are able to upregulate p53 protein in several cancer cell lines (28)(29)(30)(31)(32) and that the polyphenol-induced stabilization and expression of p53 is often associated with a G1 or G2/M phase cell cycle arrest (33). It has also been reported that tumor suppressors, like p53 and its analogs, are key molecular targets of polyphenols responsible for their pro-apoptotic effect in human and animal cancer models through the transcriptional regulation of target genes such as p21, Bax, and PUMA (32).…”

Section: Ape Induces Cell Cycle Arrest At G2/m By Downregulation Of Cmentioning

confidence: 99%

Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple and its underlying mechanisms in human breast cancer cells

D’Angelo

Martino

Ilisso

et al. 2017

International Journal of Oncology

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Among nutraceuticals, polyphenols represent the most intriguing and studied class of compounds that can be therapeutics for a large spectrum of the most common diseases, including cancer. Although polyphenols are well known as potent antioxidants, a pro-oxidant effect has been associated with a pro-apoptotic function of these compounds in various types of tumor cells. Annurca apple, a southern Italian variety, is characterized by an extremely high content of polyphenols and displays a stronger antioxidant activity compared with other varieties. In the present study we explored the antiproliferative effect of Annurca apple polyphenol extract (APE) in human breast cancer MCF-7 cells and we investigated the underlying mechanisms. Results showed that at 500 µM catechin equivalent (EqC) APE acts as a pro-oxidant increasing thiobarbituric acid-reactive species cell content of approximately 6-fold more than the untreated cells. We found that APE strongly inhibits the proliferation of MCF-7 cells by inducing G2/M cell cycle arrest and apoptosis. Immunoblot analysis demonstrated that APE treatment increases the levels of p53 and p21, downregulates the expression of the cell cycle regulatory protein cyclin D1, and inhibits ERK1/2 phosphorylation. Moreover, APE treatment caused a marked increase of pro-apoptotic Bax/Bcl-2 ratio paralleled by caspase-9, -6, -7, and poly(ADP ribose) polymerase cleavage. Altogether our data indicate that APE, at elevated concentrations, acts as a potent pro-oxidant and antiproliferative agent able to downregulate ERK1/2 pathway leading to cell cycle inhibition and apoptosis and provides a rationale for its potential use in the development of novel therapeutics towards breast cancer.

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“…Phenolic compounds due to their structural peculiarities can not only directly scavenge free radicals but also modulate oxidative stress and redox status, which is crucially important in tumorigenesis and chemoresistance. Depending on conditions they are able to implement necessary chemotherapeutic antioxidant or pro-oxidant mechanisms [ 5 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Phenolic Fractions from Vaccinium vitis-idaea L. and Their Antioxidant and Anticancer Activities Assessment

2020

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Lingonberry leaves and fruits are associated with a range of potential bioactivities related to their phenolic content and composition, but the identification of major biological activity markers remains limited. The present study aimed at the isolation of lingonberry phenolic fractions and biological activity evaluation of them. Crude dry extracts of lingonberry leaves and fruits were fractionated by chromatography using Sephadex LH-20 and analyzed by validated HPLC-PDA method. For each fraction, the anticancer activity against human clear cell renal cell carcinoma (CaKi-1), human colon adenocarcinoma (HT-29), and human malignant melanoma (IGR39) cell lines was determined using MTT assay, and the radical scavenging, reducing, and chelating activities were investigated using ABTS, FRAP, and FIC assays, respectively. Further, 28 phenolics were identified and quantified in the crude extract of lingonberry leaves and 37 in the extract of fruits. These compounds, during fractionation steps, were selectively eluted into active fractions, enriched with different groups of phenolics—monophenols, anthocyanins, phenolic acids, catechins, flavonols, or proanthocyanidins. Fractions of lingonberry leaves and fruits, obtained by the last fractionation step, proved to be the most active against tested cancer cell lines and possessed the greatest antioxidant activity. In this perspective, the predominant compounds of these fractions—polymeric and mainly A-type dimeric proanthocyanidins—also quercetin can be considered to be anticancer and antioxidant activity markers of lingonberries.

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Polyphenolic Compounds Targeting p53-Family Tumor Suppressors: Current Progress and Challenges

Abstract: Polyphenols are natural compounds characterized by a structure containing at least one benzene ring substituted by at least one hydroxyl group. Beside this chemical hallmark,

Cited by 10 publications

References 229 publications

MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro

MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro

Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple and its underlying mechanisms in human breast cancer cells

Phenolic Fractions from Vaccinium vitis-idaea L. and Their Antioxidant and Anticancer Activities Assessment

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