Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways

Sur, Subhayan; Pal, Debolina; Mandal, Santosh K.; Roy, Anup; Panda, Chinmay Kumar

doi:10.1016/j.jnutbio.2015.08.016

Cited by 48 publications

(26 citation statements)

References 44 publications

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“…WNT pathway inhibitory activity has been described for many individual polyphenols. Epigallocatechin gallate (EGCG) [ 45 ], isoquercetin [ 46 ], anthocyanins [ 47 ], theaflavin [ 48 ], ellagic acid derivatives [ 49 ], caffeoylquinic acids [ 50 ] and polymeric polyphenols [ 51 ] have all been shown to act as WNT inhibitors in many in vitro cultures of cancer cells. Some of them, like EGCG and ellagic acid, are undetectable in AAE and LAE [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations

et al. 2017

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Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP). This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i) test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv. ‘Annurca’ and Malus domestica cv ‘Limoncella’; (ii) identify the mechanisms underpinning their activities and; (iii) evaluate their potency upon gastrointestinal digestion. We here show that both Annurca and Limoncella apple extracts act as WNT inhibitors, mostly thanks to their polyphenolic contents. They inhibit the pathway in colon cells carrying FAP mutations with active dilutions falling in ranges close to consumer-relevant concentrations. Food-grade manufacturing of apple extracts increases their WNT inhibitory activity as result of the conversion of quercetin glycosides into the aglycone quercetin, a potent WNT inhibitor absent in the fresh fruit extract. However, in vitro simulated gastrointestinal digestion severely affected WNT inhibitory activity of apple extracts, as result of a loss of polyphenols. In conclusion, our results show that apple extracts inhibit the WNT pathway in colon cells carrying FAP mutations and represent a potential nutraceutical alternative for the treatment of this pathology. Enteric coating is advisable to preserve the activity of the extracts in the colon-rectal section of the digestive tract.

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Section: Discussionmentioning

confidence: 99%

WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations

et al. 2017

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“…In some studies where no optimization of GT dosage for the individual cohort was done, one would predict no effect on tumor rates might be seen and there are a small number of published rodent studies where GT did not affect tumor rates [ 4 , 15 , 16 , 17 , 18 ]. Consistent with this model is that the dosage of GT polyphenols chosen to inhibit OSCC in mice, and not be toxic, is variable ( Table 1 ), as seen with other cancers [ 8 , 12 , 94 , 95 ].…”

Section: Gt Extract and Gt Catechin Interactions With Oral And Gutmentioning

confidence: 74%

Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans

et al. 2020

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Consumption of green tea (GT) and GT polyphenols has prevented a range of cancers in rodents but has had mixed results in humans. Human subjects who drank GT for weeks showed changes in oral microbiome. However, GT-induced changes in RNA in oral epithelium were subject-specific, suggesting GT-induced changes of the oral epithelium occurred but differed across individuals. In contrast, studies in rodents consuming GT polyphenols revealed obvious changes in epithelial gene expression. GT polyphenols are poorly absorbed by digestive tract epithelium. Their metabolism by gut/oral microbial enzymes occurs and can alter absorption and function of these molecules and thus their bioactivity. This might explain the overall lack of consistency in oral epithelium RNA expression changes seen in human subjects who consumed GT. Each human has different gut/oral microbiomes, so they may have different levels of polyphenol-metabolizing bacteria. We speculate the similar gut/oral microbiomes in, for example, mice housed together are responsible for the minimal variance observed in tissue GT responses within a study. The consistency of the tissue response to GT within a rodent study eases the selection of a dose level that affects tumor rates. This leads to the theory that determination of optimal GT doses in a human requires knowledge about the gut/oral microbiome in that human.

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“…These researchers found that TF inhibits both cell lines in a concentration‐dependent manner. In a recent publication, Sur, Pal, Mandal, Roy, and Panda () examined the therapeutic and chemopreventive efficacy of tea EGCG and TF on self‐renewal Wnt and Hedgehog (Hh) pathways during CCl 4 /N‐nitosodiethylamine‐induced mouse liver carcinogenesis. The researchers discovered that TF and EGCG could restrict the development of hepatocellular carcinoma at the 30th week of carcinogen treatment showing potential chemoprevention in the continuous treated group.…”

Section: Introductionmentioning

confidence: 99%

“…These researchers found that TF inhibits both cell lines in a concentration-dependent manner. In a recent publication, Sur, Pal, Mandal, Roy, and Panda (2016) Similarly, thearubigins (TR) or polymeric black tea polyphenols (PBPs) are the oxidation products of phenolics, wherein their production accelerated after 75% conversion of catechins into flavan-3-ol molecules ( Figure 1). Thearubigins are the main abundant group of phenolic pigments in black tea which accounting for approximately 60% of the solids in a black tea infusion (Kuhnert, 2010).…”

mentioning

confidence: 99%

Inhibitory effect of black tea ( Camellia sinensis ) theaflavins and thearubigins against HCT 116 colon cancer cells and HT 460 lung cancer cells

et al. 2019

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Recently, phytochemical‐based dietary intervention has gained attention as a preventive and curative strategy against cancers owing to their safety, better tolerance, and economics. Against this background, black tea extract which contains the flavanol‐3‐ol, theaflavins (TF), and thearubigins (TR) with promising anti‐oncogenic activity were assessed to determine its in vitro inhibitory impact on colon cancer (HCT 116) and lung cancer cell lines (HT 460). In a dose‐dependent manner, results revealed that TF, TR, and their combinations cause inhibition in cell viability. However, TF imparted a maximum reduction in cell viability of HCT 116 and HT 460. Flow cytometry data revealed that TF, TR, and their combinations exhibited substantial cell arrest at the G2/M phase. The influence was more prominent in lung cancer cells (HT 460) when compared with colon cells (HCT 116). All treatments resulted in apoptosis, however, the combination of TF and TR exhibited the highest apoptotic ability in comparison to individual treatments. TF and TR exhibited a synergistic impact and significantly inhibited cell proliferation of HCT 116 and HT 460 in dose‐ and time‐dependent manners by inducing apoptosis and cell cycle arrest, wherein TF showed a more pronounced impact. Practical applications Results from the present study revealed that black tea‐isolated polyphenols (TF and TR) exhibited a significant inhibition of lung and colon cancer cell growth. A promising synergistic effect of TF and TR as inhibitors of cancer cells was observed. More clinical work, perhaps on a human subject, is needed before these two isolated compounds can be prescribed as anticancer drugs.

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Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways

Cited by 48 publications

References 44 publications

WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations

WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations

Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans

Inhibitory effect of black tea ( Camellia sinensis ) theaflavins and thearubigins against HCT 116 colon cancer cells and HT 460 lung cancer cells

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