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      (−)-Epigallocatechin-3-Gallate Inhibits Colorectal Cancer Stem Cells by Suppressing Wnt/β-Catenin Pathway

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          Abstract

          The beneficial effects of tea consumption on cancer prevention have been generally reported, while (−)-Epigallocatechin-3-gallate (EGCG) is the major active component from green tea. Cancer stem cells (CSCs) play a crucial role in the process of cancer development. Targeting CSCs may be an effective way for cancer intervention. However, the effects of EGCG on colorectal CSCs and the underlying mechanisms remain unclear. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. Immunoblotting analysis and quantitative real-time polymerase chain reaction were used to measure the alterations of critical molecules expression. Immunofluorescence staining analysis was also used to determine the expression of CD133. We revealed that EGCG inhibited the spheroid formation capability of colorectal cancer cells as well as the expression of colorectal CSC markers, along with suppression of cell proliferation and induction of apoptosis. Moreover, we illustrated that EGCG downregulated the activation of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effects of EGCG on colorectal CSCs. Taken together, this study suggested that EGCG could be an effective natural compound targeting colorectal CSCs through suppression of Wnt/β-catenin pathway, and thus may be a promising agent for colorectal cancer intervention.

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          An updated overview on Wnt signaling pathways: a prelude for more.

          Tata Rao, Michael Kühl (2010)
          Growth factor signaling is required for cellular differentiation, tissue morphogenesis, and tissue homeostasis. Misregulation of intracellular signal transduction can lead to developmental defects during embryogenesis or particular diseases in the adult. One family of growth factors important for these aspects is given by the Wnt proteins. In particular, Wnts have important functions in stem cell biology, cardiac development and differentiation, angiogenesis, cardiac hypertrophy, cardiac failure, and aging. Knowledge of growth factor signaling during differentiation will allow for improvement of targeted differentiation of embryonic or adult stem cells toward functional cardiomyocytes or for understanding the basis of diseases. Our major aim here is to provide a state of the art review summarizing our present knowledge of the intracellular Wnt-mediated signaling network. In particular, we provide evidence that the subdivision into canonical and noncanonical Wnt signaling pathways solely based on the identity of Wnt ligands or Frizzled receptors is not appropriate anymore. We thereby deliver a solid base for further upcoming articles of a review series focusing on the role of Wnt proteins on different aspects of cardiovascular development and dysfunction.
          Article 0 comments Cited 221 times – based on 0 reviews     Review now
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            Anticancer Efficacy of Polyphenols and Their Combinations

            Aleksandra Niedzwiecki, Mohd Roomi, TATIANA KALINOVSKY … (2016)
            Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB) demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP)-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract) with vitamin C, amino acids and other micronutrients (EPQ) demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM) also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion, angiogenesis, and cell growth as well as induction of apoptosis. The presence of vitamin C, amino acids and other micronutrients could enhance inhibitory effect of epigallocatechin gallate (EGCG) on secretion of MMPs. In addition, enrichment of NM with quercetin (EPQ mix) enhanced anticancer activity of NM in vivo. In conclusion, polyphenols, especially in combination with other polyphenols or micronutrients, have been shown to be effective against multiple targets in cancer development and progression, and should be considered as safe and effective approaches in cancer prevention and therapy.
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              Colon cancer stem cells: promise of targeted therapy.

              Maria Giovanna Francipane, Jan Paul Medema, Matilde Todaro … (2010)
              First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed to its epitope AC133. It is not clear if CD133 is a marker of colon CSCs-other cell surface markers, such as epithelial-specific antigen, CD44, CD166, Musashi-1, CD29, CD24, leucine-rich repeat-containing G-protein-coupled receptor 5, and aldehyde dehydrogenase 1, have been proposed. In addition to initiating and sustaining tumor growth, CSCs are believed to mediate cancer relapse after chemotherapy. How can we identify and analyze colon CSCs and what agents are being designed to kill this chemotherapy-refractory population?
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 03 June 2017
                Publication date Collection: June 2017
                Volume: 9
                Issue: 6
                Electronic Location Identifier: 572
                Affiliations
                [1 ]Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China; chenyue1005@ 123456njmu.edu.cn (Y.C.); wangxiaoqian@ 123456njmu.edu.cn (X.-Q.W.); qizhang3036@ 123456njmu.edu.cn (Q.Z.); njmuzhujy@ 123456njmu.edu.cn (J.-Y.Z.); yuanli0321@ 123456njmu.edu.cn (Y.L.); xiechunfeng932@ 123456njmu.edu.cn (C.-F.X.); xiaotingli@ 123456njmu.edu.cn (X.-T.L.); jwu@ 123456njmu.edu.cn (J.-S.W.); gss9814@ 123456njmu.edu.cn (S.-S.G.)
                [2 ]The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
                [3 ]Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China
                Author notes
                [* ]Correspondence: cyzhong@ 123456njmu.edu.cn (C.-Y.Z.); hanhy@ 123456sysucc.org.cn (H.-Y.H.)
                Article
                Publisher ID: nutrients-09-00572
                DOI: 10.3390/nu9060572
                PMC ID: 5490551
                PubMed ID: 28587207
                SO-VID: ed5c05c4-7c0f-4971-b0db-8ca6550d5255
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 05 April 2017
                Date accepted : 30 May 2017
                Categories
                Subject: Article

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: egcg,colorectal cancer stem cells,wnt/β-catenin pathway
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: egcg, colorectal cancer stem cells, wnt/β-catenin pathway

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