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Xiao X, Jian Y, Jiang Y, Wei S, Song W. Condensed tannins from Salix babylonica L. leaves induce apoptosis of human ovarian cancer cells through mitochondrial and PI3K/AKT/ERK signaling pathways. Int J Biol Macromol 2025; 309:142635. [PMID: 40158587 DOI: 10.1016/j.ijbiomac.2025.142635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 03/20/2025] [Accepted: 03/27/2025] [Indexed: 04/02/2025]
Abstract
Condensed tannins, natural antioxidants, are widely known for their antitumor activity with low toxicity. However, the antitumor mechanism of Salix babylonica leaf condensed tannins (SCTs) remains unclear. Here, we purified bioactive SCTs and analyzed their structural characteristics, antitumor effects on human ovarian cancer (OC) cells as well as related potential mechanism. FT-IR, ESI-MS, and HPLC analyses demonstrated that SCTs primarily consist of procyanidins with (epi)catechin as the main flavan-3-ol extension unit. SCTs significantly inhibited the proliferation and migration of OVCAR3 and A2780 cells, induced G0/G1 cell cycle arrest, and promoted apoptosis. SCTs induced apoptosis through the mitochondrial apoptotic pathway by decreasing mitochondrial membrane potential, increasing intracellular reactive oxygen species generation, elevating the Bax/Bcl-2 ratio, and activating caspase-3. Network pharmacology analysis speculated that SCTs exert anti-ovarian cancer effects by targeting multiple targets and pathways, among which the PI3K/AKT/ERK pathway may be the main pathway of action. Western blot confirmed that SCTs inhibited the phosphorylation of AKT, MEK, and ERK. Moreover, SCTs dose-dependently impaired OVCAR3 tumor spheroid growth in three-dimensional culture models. These results suggested that SCTs induced apoptosis in OC cells by activating the mitochondrial-associated apoptosis pathway and inhibiting the PI3K/AKT/ERK signaling pathway, showing potential as therapeutic agents for OC.
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Affiliation(s)
- Xiaoxue Xiao
- College of Life Science, Yangtze University, Jingzhou 434023, China; School of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan 467036, China
| | - Yanbo Jian
- College of Life Science, Yangtze University, Jingzhou 434023, China; School of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan 467036, China
| | - Yu Jiang
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, China
| | - Shudong Wei
- College of Life Science, Yangtze University, Jingzhou 434023, China.
| | - Wei Song
- School of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan 467036, China; Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou 450000, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
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2
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Xing Z, Fei X, Chen S, Gong D, Hu X, Zhang G. Covalent interaction of ovalbumin with proanthocyanidins improves its thermal stability and antioxidant and emulsifying activity. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:890-900. [PMID: 39271480 DOI: 10.1002/jsfa.13881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/20/2024] [Accepted: 08/29/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND The structure of proanthocyanidins (PC) contains a large number of active phenolic hydroxyl groups, which makes it have strong antioxidant capacity. This study investigated the structural and functional properties of ovalbumin (OVA) modified by its interaction with PC. RESULTS It was found that on increasing the concentration ratio of PC to OVA from 10:1 to 40:1, the free amino and total sulfhydryl contents of OVA decreased from 470.59 ± 38.77 and 29.81 ± 0.31 nmol mg-1 to 96.61 ± 4.55 and 21.22 ± 0.78 nmol mg-1, respectively, and the free sulfhydryl content increased from 7.65 ± 0.41 to 9.48 ± 0.58 nmol mg-1. These results indicated that CN and CS bonds were formed and PC was covalently linked with OVA. The PC content in the OVA-PC conjugates increased from 281.93 ± 12.92 to 828.81 ± 46.09 nmol mg-1 on increasing the concentration ratio of PC to OVA from 10:1 to 40:1. The contents of α-helix and β-turn of OVA decreased, and the contents of β-sheet and random coil increased, confirmed by circular dichroism. The tertiary structure of OVA was also altered according to the results of fluorescence and ultraviolet absorption spectra. The surface hydrophobicity of OVA-PC conjugates decreased with increasing bound polyphenol content. The conjugation of OVA to PC significantly improved its emulsification and antioxidant activity and denaturation temperature. CONCLUSION This study may provide valuable information for improving OVA's functional properties and its PC conjugates for applications in the food industry. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Zenghong Xing
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Xiaoyun Fei
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Shuling Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Deming Gong
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Xing Hu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Guowen Zhang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
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3
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Zhu W, Oteiza PI. NADPH oxidase 1: A target in the capacity of dimeric ECG and EGCG procyanidins to inhibit colorectal cancer cell invasion. Redox Biol 2023; 65:102827. [PMID: 37516013 PMCID: PMC10410180 DOI: 10.1016/j.redox.2023.102827] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/20/2023] [Accepted: 07/21/2023] [Indexed: 07/31/2023] Open
Abstract
Colorectal cancer (CRC) is prevalent worldwide. Dietary consumption of procyanidins has been linked to a reduced risk of developing CRC. The epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequently dysregulated in CRC. Our earlier research showed that the procyanidin dimers of epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), through their interaction with lipid rafts, inhibit the EGFR signaling pathway and decrease CRC cell growth. The process of cancer cell invasion and metastasis involves matrix metalloproteinases (MMPs), which are partially EGFR-regulated. This study investigated whether ECG and EGCG dimers can inhibit EGF-induced CRC cell invasion by suppressing the redox-regulated activation of the EGFR/MMPs pathway. Both dimers mitigated EGF-induced cell invasion and the associated increase of MMP-2/9 expression and activity in different CRC cell lines. In Caco-2 cells, both dimers inhibited the activation of the EGFR and downstream of NF-κB, ERK1/2 and Akt, which was associated with decreased MMP-2/9 transcription. EGF induced a rapid NOX1-dependent oxidant increase, which was diminished by both ECG and EGCG dimers and NOX inhibitors (apocynin, Vas-2870, DPI). Both dimers inhibited NOX1 gene expression, as well as NOX1 activity with evidence of direct binding to NOX1. Both dimers, all NOX chemical inhibitors and NOX1 silencing inhibited EGF-mediated activation of the EGFR signaling pathway and the increased MMP-2/9 mRNA levels and activity. Pointing to the relevance of NOX1 on ECG and EGCG dimer effects on CRC invasiveness, silencing of NOX1 also inhibited EGF-stimulated Caco-2 cell invasion. In summary, ECG and EGCG dimers can act inhibiting CRC cell invasion/metastasis both, by downregulating MMP-2 and MMP-9 expression via a NOX1/EGFR-dependent mechanism, and through a direct inhibitory effect on MMPs enzyme activity.
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Affiliation(s)
- Wei Zhu
- Department of Nutrition, University of California, Davis, CA, USA
| | - Patricia I Oteiza
- Department of Nutrition, University of California, Davis, CA, USA; Department of Environmental Toxicology, University of California, Davis, CA, USA.
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4
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Speciani MC, Gargari G, Penagini R, Mutignani M, Ferraroni M, Natale A, Katsoulis M, Cintolo M, Leone P, Airoldi A, Vecchi M, Bonzi R, Ciafardini C, Oreggia B, Carnevali P, Guglielmetti S, Riso P, La Vecchia C, Rossi M. Garlic consumption in relation to colorectal cancer risk and to alterations of blood bacterial DNA. Eur J Nutr 2023:10.1007/s00394-023-03110-2. [PMID: 37093261 DOI: 10.1007/s00394-023-03110-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 01/31/2023] [Indexed: 04/25/2023]
Abstract
PURPOSE Garlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood. METHODS We conducted a case-control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann-Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence. RESULTS The OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11-0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus. CONCLUSIONS The study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.
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Affiliation(s)
- Michela Carola Speciani
- Branch of Medical Statistics, Biometry, and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Via Celoria 22, 20133, Milan, Italy
| | - Giorgio Gargari
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Massimiliano Mutignani
- Digestive and Interventional Endoscopy Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Monica Ferraroni
- Branch of Medical Statistics, Biometry, and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Via Celoria 22, 20133, Milan, Italy
| | - Arianna Natale
- Branch of Medical Statistics, Biometry, and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Via Celoria 22, 20133, Milan, Italy
| | - Michail Katsoulis
- MRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, UCL, London, UK
| | - Marcello Cintolo
- Digestive and Interventional Endoscopy Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Pierfrancesco Leone
- General Surgery Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Aldo Airoldi
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Rossella Bonzi
- Branch of Medical Statistics, Biometry, and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Via Celoria 22, 20133, Milan, Italy
| | - Clorinda Ciafardini
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - Barbara Oreggia
- General Surgery Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pietro Carnevali
- Division of Minimally-Invasive Surgical Oncology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Simone Guglielmetti
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Patrizia Riso
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Carlo La Vecchia
- Branch of Medical Statistics, Biometry, and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Via Celoria 22, 20133, Milan, Italy
| | - Marta Rossi
- Branch of Medical Statistics, Biometry, and Epidemiology "G. A. Maccacaro", Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Via Celoria 22, 20133, Milan, Italy.
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Rubert J, Gatto P, Pancher M, Sidarovich V, Curti C, Mena P, Del Rio D, Quattrone A, Mattivi F. A Screening of Native (Poly)phenols and Gut-Related Metabolites on 3D HCT116 Spheroids Reveals Gut Health Benefits of a Flavan-3-ol Metabolite. Mol Nutr Food Res 2022; 66:e2101043. [PMID: 35394679 PMCID: PMC9787721 DOI: 10.1002/mnfr.202101043] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 03/19/2022] [Indexed: 12/30/2022]
Abstract
SCOPE Epidemiological evidence suggests that a reduced risk of colorectal cancer (CRC) is correlated with high consumption of fruits and vegetables, which are major sources of fiber and phytochemicals, such as flavan-3-ols. However, it remains unknown how these phytochemicals and their specific gut-related metabolites may alter cancer cell behavior. METHODS AND RESULTS A focused screening using native (poly)phenols and gut microbial metabolites (GMMs) on 3D HCT116 spheroids is carried out using a high-throughput imaging approach. Dose-responses, IC50 , and long-term exposure are calculated for the most promising native (poly)phenols and GMMs. As a result, this research shows that (poly)phenol catabolites may play a key role in preventing cancer propagation. Indeed, µM concentration levels of (4R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone significantly decrease spheroid size at early stages of spheroid aggregation and gene expression of matrix metalloproteinases. CONCLUSION A chronic exposure to (4R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone may lead to a reduced CRC risk. Daily intake of monomeric, oligomeric, and polymeric flavan-3-ols may increase the colonic concentrations of this metabolite, and, in turn, this compound may act locally interacting with intestinal epithelial cells, precancerous and cancer cells.
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Affiliation(s)
- Josep Rubert
- Food Quality and DesignWageningen University & ResearchBornse Weilanden 9Wageningen6708 WGThe Netherlands
- Division of Human Nutrition and HealthWageningen University & ResearchStippeneng 4Wageningen6708 WEThe Netherlands
| | - Pamela Gatto
- HTS and Validation Core FacilityDept. CIBIO ‐ Department of CellularComputational and Integrative BiologyUniversity of TrentoVia Sommarive 9Trento38123Italy
| | - Michael Pancher
- HTS and Validation Core FacilityDept. CIBIO ‐ Department of CellularComputational and Integrative BiologyUniversity of TrentoVia Sommarive 9Trento38123Italy
| | - Viktoryia Sidarovich
- HTS and Validation Core FacilityDept. CIBIO ‐ Department of CellularComputational and Integrative BiologyUniversity of TrentoVia Sommarive 9Trento38123Italy
| | - Claudio Curti
- Department of Food and DrugUniversity of ParmaParco Area delle Scienze, 27/AParma43124Italy
| | - Pedro Mena
- Human Nutrition UnitDepartment of Food and DrugUniversity of ParmaMedical School Building C, Via Volturno, 39Parma43125Italy
- Microbiome Research HubUniversity of ParmaParma43124Italy
| | - Daniele Del Rio
- Human Nutrition UnitDepartment of Food and DrugUniversity of ParmaMedical School Building C, Via Volturno, 39Parma43125Italy
- Microbiome Research HubUniversity of ParmaParma43124Italy
- School of Advanced Studies on Food and NutritionUniversity of ParmaParma43126Italy
| | - Alessandro Quattrone
- Laboratory of Translational GenomicsDept. CIBIO ‐ Department of CellularComputational and Integrative BiologyUniversity of TrentoVia Sommarive 9Trento38123Italy
| | - Fulvio Mattivi
- Dept. CIBIO ‐ Department of CellularComputational and Integrative BiologyUniversity of TrentoVia Sommarive 9Trento38123Italy
- Metabolomics UnitDepartment of Food Quality and NutritionFondazione Edmund Mach ‐ FEMResearch and Innovation CentreVia Mach 1San Michele all'Adige38098Italy
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Ren Y, Qin Z, Wang Z, Wei S, Chen H, Zhu T, Liu L, Zhao Y, Ding B, Song W. Condensed tannins from
Ulmus pumila
L. leaves induce
G2
/M phase arrest and apoptosis via caspase‐cascade activation in
TFK
‐1 cholangiocarcinoma cells. J Food Biochem 2022; 46:e14374. [DOI: 10.1111/jfbc.14374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 06/06/2022] [Accepted: 06/23/2022] [Indexed: 12/01/2022]
Affiliation(s)
- Yuanjing Ren
- College of Life Science Yangtze University Jingzhou China
- College of Life Science and Engineering Henan University of Urban Construction Pingdingshan China
| | - Zeya Qin
- College of Life Science Yangtze University Jingzhou China
| | - Zhanchang Wang
- Forestry and Fruit Tree Research Institute Wuhan Academy of Agricultural Sciences Wuhan China
| | - Shudong Wei
- College of Life Science Yangtze University Jingzhou China
| | - Hui Chen
- College of Life Science Yangtze University Jingzhou China
| | - Tao Zhu
- College of Life Science and Engineering Henan University of Urban Construction Pingdingshan China
| | - Lulu Liu
- College of Life Science Yangtze University Jingzhou China
| | - Yaying Zhao
- College of Life Science Yangtze University Jingzhou China
| | - Baomiao Ding
- College of Life Science Yangtze University Jingzhou China
| | - Wei Song
- College of Life Science and Engineering Henan University of Urban Construction Pingdingshan China
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Proanthocyanidins and Where to Find Them: A Meta-Analytic Approach to Investigate Their Chemistry, Biosynthesis, Distribution, and Effect on Human Health. Antioxidants (Basel) 2021; 10:antiox10081229. [PMID: 34439477 PMCID: PMC8389005 DOI: 10.3390/antiox10081229] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 12/22/2022] Open
Abstract
Proanthocyanidins (PACs) are a class of polyphenolic compounds that are attracting considerable interest in the nutraceutical field due to their potential health benefits. However, knowledge about the chemistry, biosynthesis, and distribution of PACs is limited. This review summarizes the main chemical characteristics and biosynthetic pathways and the main analytical methods aimed at their identification and quantification in raw plant matrices. Furthermore, meta-analytic approaches were used to identify the main plant sources in which PACs were contained and to investigate their potential effect on human health. In particular, a cluster analysis identified PACs in 35 different plant families and 60 different plant parts normally consumed in the human diet. On the other hand, a literature search, coupled with forest plot analyses, highlighted how PACs can be actively involved in both local and systemic effects. Finally, the potential mechanisms of action through which PACs may impact human health were investigated, focusing on their systemic hypoglycemic and lipid-lowering effects and their local anti-inflammatory actions on the intestinal epithelium. Overall, this review may be considered a complete report in which chemical, biosynthetic, ecological, and pharmacological aspects of PACs are discussed.
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Machado APDF, Geraldi MV, do Nascimento RDP, Moya AMTM, Vezza T, Diez-Echave P, Gálvez JJ, Cazarin CBB, Maróstica Júnior MR. Polyphenols from food by-products: An alternative or complementary therapy to IBD conventional treatments. Food Res Int 2021; 140:110018. [PMID: 33648249 DOI: 10.1016/j.foodres.2020.110018] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel diseases (IBD) are illnesses characterized by chronic intestinal inflammation and microbial dysbiosis that have emerged as a public health challenge worldwide. It comprises two main conditions: Crohn's disease and ulcerative colitis. Currently, conventional therapy to treat IBD are not free from side effects, such as liver and kidney toxicity, drug resistance, and allergic reactions. In view of this, there is growing research for alternative and complementary therapies that, in addition to acting in the prevention or the control of the disease, do not compromise the quality of life and health of individuals. In this sense, a growing body of evidence has confirmed the benefits of natural phenolic compounds in intestinal health. Phenolic compounds or polyphenols are molecules widely distributed throughout the plant kingdom (flowers, vegetables, leaves, and fruits), including plant materials remaining of the handling and food industrial processing, referred to in the scientific literature as by-products, food waste, or bagasse. Since by-products are low-cost, abundant, easily accessible, safe, and rich in bioactive compounds, it becomes an exciting option to extract, concentrate or isolate phenolic compounds to be posteriorly applied in the therapeutic approach of IBD. In this article, we have reviewed the main phenolic compounds present in various plants and by-products that have shown beneficial and/or promising effects in experimental pre-clinical, clinical, and in vitro research with IBD. In addition, we have mentioned and suggested several plants and by-products originated and produced in Latin America that could be part of future research as good sources of specific phenolic compounds to be applied in the prevention and development of alternative treatments for IBD. This review may offer a valuable reference for studies related to IBD administering phenolic compounds from natural, cheap, and easily accessible raw and undervalued materials.
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Affiliation(s)
| | - Marina Vilar Geraldi
- University of Campinas, School of Food Engineering, 80 Monteiro Lobato Street, 13083-862 Campinas, SP, Brazil
| | | | | | - Teresa Vezza
- University of Granada, Department of Pharmacology, CIBER-EHD, Institute of Biosanitary Research of Granada (ibs.GRANADA), Biomedical Research Center (CIBM), Campus de la Salud, 18071 Granada, Spain
| | - Patricia Diez-Echave
- University of Granada, Department of Pharmacology, CIBER-EHD, Institute of Biosanitary Research of Granada (ibs.GRANADA), Biomedical Research Center (CIBM), Campus de la Salud, 18071 Granada, Spain
| | - Julio Juan Gálvez
- University of Granada, Department of Pharmacology, CIBER-EHD, Institute of Biosanitary Research of Granada (ibs.GRANADA), Biomedical Research Center (CIBM), Campus de la Salud, 18071 Granada, Spain
| | - Cinthia Bau Betim Cazarin
- University of Campinas, School of Food Engineering, 80 Monteiro Lobato Street, 13083-862 Campinas, SP, Brazil
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9
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Daveri E, Adamo AM, Alfine E, Zhu W, Oteiza PI. Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway. Redox Biol 2021; 38:101830. [PMID: 33338921 PMCID: PMC7750420 DOI: 10.1016/j.redox.2020.101830] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/04/2020] [Accepted: 12/07/2020] [Indexed: 01/08/2023] Open
Abstract
Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs.
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Affiliation(s)
- Elena Daveri
- Departments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA; Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133, Milan, Italy
| | - Ana M Adamo
- Department of Biological Chemistry and IQUIFIB (UBA-CONICET), Facultad de Farmacia y Bioquímica, 1113, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Eugenia Alfine
- Departments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA
| | - Wei Zhu
- Departments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA
| | - Patricia I Oteiza
- Departments of Nutrition University of California, Davis, 95616, Davis, CA, USA; Departments of Environmental Toxicology, University of California, Davis, 95616, Davis, CA, USA.
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10
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Pomological, Sensorial, Nutritional and Nutraceutical Profile of Seven Cultivars of Cherimoya ( Annona cherimola Mill). Foods 2020; 10:foods10010035. [PMID: 33374394 PMCID: PMC7823484 DOI: 10.3390/foods10010035] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 01/05/2023] Open
Abstract
In this work, the food quality of four international (Campas, Chaffey, Fino de Jete and White) and three local (Daniela, Torre1 and Torre2) cultivars of Cherimoya (Annona cherimola Mill) was investigated. With this aim, pomological traits, sensorial attributes, physiochemical parameters (pH, total soluble content and total acidity), nutritional composition (macro- and micro-nutrients) and nutraceutical values (bioactive compounds, radical scavenging and antioxidant properties) were evaluated. Among the seven observed cultivars, Fino de Jete was identified as the best, not only for its commercial attributes such as pomological traits and physiochemical values, but also for its nutritional composition. On the other hand, Chaffey and Daniela were the cultivars with the highest content of polyphenols, proanthocyanidins, and with the strongest antioxidant capacity. Concerning the two local ecotypes, Torre1 and Torre2, they displayed a balanced nutritional profile that, if combined with their discrete nutraceutical, physicochemical and pomological values, may result in a reassessment of their commercial impact. In conclusion, our data provide interesting information about the pomological, nutritional, and nutraceutical properties of cherimoya fruits. Our results, in addition to promoting the commercial impact of local cultivars, may increase the use of individual cultivars in breeding programs.
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Zhu W, Li MC, Wang FR, Mackenzie GG, Oteiza PI. The inhibitory effect of ECG and EGCG dimeric procyanidins on colorectal cancer cells growth is associated with their actions at lipid rafts and the inhibition of the epidermal growth factor receptor signaling. Biochem Pharmacol 2020; 175:113923. [PMID: 32217102 PMCID: PMC7489796 DOI: 10.1016/j.bcp.2020.113923] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 03/19/2020] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. Epidemiological studies indicate that consumption of fruits and vegetables containing procyanidins is associated with lower CRC risk. This study investigated the capacity of two dimeric procyanidins composed of epicatechin gallate (ECG) or epigallocatechin gallate (EGCG) isolated from persimmons, to inhibit CRC cell growth and promote apoptosis, characterizing the underlying mechanisms. ECG and EGCG dimers reduced the growth of five human CRC cell lines in a concentration (10-60 μM)- and time (24-72 h)-dependent manner, with a 72 h-IC50 value in Caco-2 cells of 10 and 30 μM, respectively. ECG and EGCG dimers inhibited Caco-2 cell proliferation by arresting the cell cycle in G2/M phase and by inducing apoptosis via the mitochondrial pathway. In addition, ECG and EGCG dimers inhibited cell migration, invasion, and adhesion, decreasing the activity of matrix metalloproteinases (MMP-2/9). Mechanistically, ECG and EGCG dimers inhibited the activation of lipid raft-associated epidermal growth factor (EGF) receptor (EGFR), without affecting its localization at lipid rafts. In particular, ECG and EGCG dimers reduced EGFR phosphorylation at Tyr1068 residue, prevented EGFR dimerization and activation upon stimulation, and induced EGFR internalization both in the absence and presence of EGF. Furthermore, ECG and EGCG dimers increased EGFR phosphorylation at Tyr1045 residue, providing a docking site for ubiquitin ligase c-Cbl and induced EGFR degradation by the proteasome. Downstream of EGFR, ECG and EGCG dimers inhibited the activation of the MEK/ERK1/2 and PI3K/AKT signaling pathways, downregulating proteins involved in the modulation of cell survival. In conclusion, ECG and EGCG dimers reduced CRC cell growth by inhibiting EGFR activation at multiple steps, including the disruption of lipid rafts integrity and promoting EGFR degradation. These results shed light on a potential molecular mechanism on how procyanidins-rich diets may lower CRC risk.
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Affiliation(s)
- Wei Zhu
- Department of Nutrition, University of California, Davis, CA, USA; Department of Environmental Toxicology, University of California, Davis, CA, USA; College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Mei C Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Feng R Wang
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China
| | | | - Patricia I Oteiza
- Department of Nutrition, University of California, Davis, CA, USA; Department of Environmental Toxicology, University of California, Davis, CA, USA.
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12
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Guardado Yordi E, Koelig R, Matos MJ, Pérez Martínez A, Caballero Y, Santana L, Pérez Quintana M, Molina E, Uriarte E. Artificial Intelligence Applied to Flavonoid Data in Food Matrices. Foods 2019; 8:E573. [PMID: 31739559 PMCID: PMC6915672 DOI: 10.3390/foods8110573] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/25/2019] [Accepted: 10/29/2019] [Indexed: 11/30/2022] Open
Abstract
Increasing interest in constituents and dietary supplements has created the need for more efficient use of this information in nutrition-related fields. The present work aims to obtain optimal models to predict the total antioxidant properties of food matrices, using available information on the amount and class of flavonoids present in vegetables. A new dataset using databases that collect the flavonoid content of selected foods has been created. Structural information was obtained using a structural-topological approach called TOPological Sub-Structural Molecular (TOPSMODE). Different artificial intelligence algorithms were applied, including Machine Learning (ML) methods. The study allowed us to demonstrate the effectiveness of the models using structural-topological characteristics of dietary flavonoids. The proposed models can be considered, without overfitting, effective in predicting new values of Oxygen Radical Absorption capacity (ORAC), except in the Multi-Layer Perceptron (MLP) algorithm. The best optimal model was obtained by the Random Forest (RF) algorithm. The in silico methodology we developed allows us to confirm the effectiveness of the obtained models, by introducing the new structural-topological attributes, as well as selecting those that most influence the class variable.
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Affiliation(s)
- Estela Guardado Yordi
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Raúl Koelig
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
| | - Maria J. Matos
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
| | - Amaury Pérez Martínez
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
- Facultad de Ciencias de la Tierra, Universidad Estatal Amazónica, km 2 ½ vía Puyo a Tena (Paso Lateral), Puyo 032892-118, Ecuador
| | - Yailé Caballero
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
| | - Lourdes Santana
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Manuel Pérez Quintana
- Facultad de Ciencias de la Tierra, Universidad Estatal Amazónica, km 2 ½ vía Puyo a Tena (Paso Lateral), Puyo 032892-118, Ecuador
| | - Enrique Molina
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Eugenio Uriarte
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- Instituto de Ciencias Químicas Aplicadas, Universidad Autónoma de Chile, Santiago 7500912, Chile
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Zou YC, Wu CL, Ma CF, He S, Brennan CS, Yuan Y. Interactions of grape seed procyanidins with soy protein isolate: Contributing antioxidant and stability properties. Lebensm Wiss Technol 2019. [DOI: 10.1016/j.lwt.2019.108465] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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14
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Zhang R, Yu Q, Lu W, Shen J, Zhou D, Wang Y, Gao S, Wang Z. Grape seed procyanidin B2 promotes the autophagy and apoptosis in colorectal cancer cells via regulating PI3K/Akt signaling pathway. Onco Targets Ther 2019; 12:4109-4118. [PMID: 31213831 PMCID: PMC6538883 DOI: 10.2147/ott.s195615] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 03/07/2019] [Indexed: 12/17/2022] Open
Abstract
Aim: Colorectal cancer (CRC) is a major malignancy in China, which is the critical risk of people health. Many natural herbs extracts have been found to exhibit good therapeutic effect on CRC. Our previous study found that grape seed procyanidins B2 (PB2) would induce CRC cell death. However, the molecular mechanism underlying its anti-tumor effect on CRC remains unclear. Thereby, this study aimed to investigate the anti-tumor mechanism of PB2 on CRC. Methods: CCK-8, western blotting, flow cytometry, qRT-PCR and animal study were used in the current study. Results: The in vitro and in vivo data demonstrated that PB2 could promote the apoptosis of CRC cells in a dose-dependent manner, which was significantly reversed by caspase 3 inhibitor. Meanwhile, PB2 dose-dependently induced autophagy in CRC cells, which was markedly attenuated by autophagy inhibitor 3-MA. In addition, PB2 dose-dependently inhibited the expressions of p-PI3K, p-Akt and p-mTOR in the cells. Conclusion: PB2 dose-dependently induced apoptosis and autophagy in CRC cells via downregulation of PI3K/Akt pathway. This study provided the experimental basis for further development of PB2 as a new effective anticancer drug for the patients with CRC.
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Affiliation(s)
- Ruijuan Zhang
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
| | - Qianyun Yu
- Department of TCM, Shanghai Huangpu District Wuliqiao Community Health Center, Shanghai, 200023, People's Republic of China
| | - Wenqiang Lu
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
| | - Jun Shen
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
| | - Dongqing Zhou
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
| | - Yingjue Wang
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
| | - Shurong Gao
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
| | - Zhijun Wang
- Department of TCM, Shanghai Putuo District People's Hospital, Shanghai 200060, People's Republic of China
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Afshari K, Haddadi NS, Haj-Mirzaian A, Farzaei MH, Rohani MM, Akramian F, Naseri R, Sureda A, Ghanaatian N, Abdolghaffari AH. Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies. J Cell Physiol 2019; 234:21519-21546. [PMID: 31087338 DOI: 10.1002/jcp.28777] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 04/07/2019] [Accepted: 04/11/2019] [Indexed: 12/18/2022]
Abstract
Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti-inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.
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Affiliation(s)
- Khashayar Afshari
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Nazgol-Sadat Haddadi
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Arvin Haj-Mirzaian
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Mojtaba Rohani
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Freshteh Akramian
- Department of Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Rozita Naseri
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands, Palma de Mallorca, Spain.,CIBEROBN (Physiopathology of Obesity and Nutrition, CB12/03/30038), Instituto de Salud Carlos III, Madrid, Spain
| | - Negar Ghanaatian
- Department of Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Amir Hossein Abdolghaffari
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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16
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Wang W, Zhan L, Guo D, Xiang Y, Zhang Y, Tian M, Han Z. Transcriptome analysis of pancreatic cancer cell response to treatment with grape seed proanthocyanidins. Oncol Lett 2018; 17:1741-1749. [PMID: 30675233 PMCID: PMC6341838 DOI: 10.3892/ol.2018.9807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 10/25/2018] [Indexed: 01/09/2023] Open
Abstract
Grape seed proanthocyanidins (GSPs) have been demonstrated to exhibit potential chemotherapeutic efficacy against various cancer types. To determine the underlying molecular mechanisms involved in GSP-induced apoptosis, the present study prepared pancreatic cancer (PC) cells samples, S3, S12 and S24, which were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control cell samples, C3, C12 and C24, were also prepared. Using RNA-sequencing, transcriptome comparisons were performed, which identified 966, 3,543 and 4,944 differentially-expressed genes (DEGs) in S3 vs. C3, S12 vs. C12 and S24 vs. C24, respectively. Gene Ontology analysis of the DEGs, revealed that treatment with GSPs is associated with disruption of the cell cycle (CC) in PC cells. Additionally, disruption of transcription, DNA replication and DNA repair were associated with GSP-treatment in PC cells. Network analysis demonstrated that the common DEGs involved in the CC, transcription, DNA replication and DNA repair were integrated, and served essential roles in the control of CC progression in cancer cells. In summary, GSPs may exhibit a potential chemotherapeutic effect on PC cell proliferation.
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Affiliation(s)
- Weihua Wang
- Department of Food Science, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, P.R. China.,Xinjiang Production and Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, Alar, Xinjiang 843300, P.R. China
| | - Leilei Zhan
- Center for Genome Analysis, ABLife Inc., Wuhan, Hubei 430075, P.R. China
| | - Dongqi Guo
- Department of Food Science, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, P.R. China.,Xinjiang Production and Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, Alar, Xinjiang 843300, P.R. China
| | - Yanju Xiang
- Department of Food Science, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, P.R. China.,Xinjiang Production and Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, Alar, Xinjiang 843300, P.R. China
| | - Yu Zhang
- Center for Genome Analysis, ABLife Inc., Wuhan, Hubei 430075, P.R. China
| | - Muxing Tian
- Department of Food Science, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, P.R. China.,Xinjiang Production and Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, Alar, Xinjiang 843300, P.R. China
| | - Zhanjiang Han
- Department of Food Science, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, P.R. China.,Xinjiang Production and Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Alar, Xinjiang 843300, P.R. China
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17
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Oteiza P, Fraga C, Mills D, Taft D. Flavonoids and the gastrointestinal tract: Local and systemic effects. Mol Aspects Med 2018; 61:41-49. [DOI: 10.1016/j.mam.2018.01.001] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 01/04/2018] [Accepted: 01/05/2018] [Indexed: 12/25/2022]
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18
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Flavan-3-ols consumption and cancer risk: A meta-analysis of epidemiologic studies. Oncotarget 2018; 7:73573-73592. [PMID: 27634884 PMCID: PMC5342000 DOI: 10.18632/oncotarget.12017] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 07/27/2016] [Indexed: 02/05/2023] Open
Abstract
Although numerous in vitro studies and animal model data have suggested that flavan-3-ols, the most common subclass of flavonoids in the diet, may exert protective effects against cancer, epidemiologic studies have reported inconclusive results for the association between flavan-3-ols intake and cancer risk. Therefore, we conducted this meta-analysis of epidemiologic studies to investigate the preventive effects of flavan-3-ols on various types of cancers. A total of 43 epidemiologic studies, consisting of 25 case-control and 18 prospective cohort studies, were included. A significant inverse association was shown between flavan-3-ols intake and the risk of overall cancer (relative risk (RR) 0.935, 95%CI: 0.891-0.981). When cancer types were separately analyzed, a statistically significant protective effect of flavan-3-ols consumption was observed in rectal cancer (RR 0.838, 95%CI: 0.733-0.958), oropharyngeal and laryngeal cancer (RR 0.759, 95%CI: 0.581-0.993), breast (RR 0.885, 95%CI: 0.790-0.991) in case-control studies and stomach cancer in women (RR 0.633, 95%CI: 0.468-0.858). Our analysis indicates the potential benefits of flavan-3-ols in cancer prevention.
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19
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He X, Sun LM. Dietary intake of flavonoid subclasses and risk of colorectal cancer: evidence from population studies. Oncotarget 2018; 7:26617-27. [PMID: 27058896 PMCID: PMC5042003 DOI: 10.18632/oncotarget.8562] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 03/10/2016] [Indexed: 12/18/2022] Open
Abstract
Objective To systematically evaluate the relationship between flavonoids intake and colorectal cancer risk by conducting a meta-analysis. Results Our meta-analysis included 18 studies involving 16,917 colorectal cancer cases in 559,486 participants in relations to flavonoids intake during six to twenty-six years of follow-up. Our results indicated that specific flavonoid subclasses, such as procyanidins (OR = 0.75; 95% CI, 0.66–0.86) and isoflavones (OR = 0.87; 95% CI, 0.78–0.98), showed protective effects against colorectal cancer risk. There was no enough evidence indicating that increased consumption of total flavonoids were significantly associated with reduced risk of colorectal cancer (OR = 0.94, 95% CI, 0.81–1.09). There was no publication bias across studies. Methods We performed a systematic search of PubMed, Web of Science and the Cochrane Library databases for relevant articles before December 2015. A random-effects model was used to estimate summary odds ratios and 95% confidence intervals (CIs) for associations between flavonoids and colorectal cancer risk. We assessed heterogeneity among studies by the Cochran Q and I2 statistics. Conclusions Our meta-analysis provides comprehensive evidence and partly supported the hypothesis that higher habitual intake of foods rich in procyanidins and isoflavones may potentially decrease colorectal cancer incidence. More prospective studies are warranted to verify this protective association.
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Affiliation(s)
- Xingkang He
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University Medical School, Hangzhou 310016, China.,Institute of Gastroenterology, Zhejiang University (IGZJU), Hangzhou 310016, China
| | - Lei-Min Sun
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University Medical School, Hangzhou 310016, China.,Institute of Gastroenterology, Zhejiang University (IGZJU), Hangzhou 310016, China
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Zhao Y, Hu X, Zuo X, Wang M. Chemopreventive effects of some popular phytochemicals on human colon cancer: a review. Food Funct 2018; 9:4548-4568. [DOI: 10.1039/c8fo00850g] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The present review summarizes (1) the epidemiology and etiology of colon cancer, (2) generalized cancer chemoprotective mechanisms, and (3) the chemopreventive properties of some popular phytochemicals as well as some phytochemicals developed by our research group recently.
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Affiliation(s)
- Yueliang Zhao
- College of Food Science and Technology
- Shanghai Ocean University
- Shanghai
- China
- Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai)
| | - Xiaoqian Hu
- College of Food Science and Technology
- Shanghai Ocean University
- Shanghai
- China
- Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai)
| | - Xinyuan Zuo
- School of Petroleum and Chemical Engineering
- Dalian University of Technology
- Panjin City
- China
| | - Mingfu Wang
- College of Food Science and Technology
- Shanghai Ocean University
- Shanghai
- China
- Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai)
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Abstract
Nut consumption is clearly related to human health outcomes. Its beneficial effects have been mainly attributed to nut fatty acid profiles and content of vegetable protein, fiber, vitamins, minerals, phytosterols and phenolics. However, in this review we focus on the prebiotics properties in humans of the non-bioaccessible material of nuts (polymerized polyphenols and polysaccharides), which provides substrates for the human gut microbiota and on the formation of new bioactive metabolites and the absorption of that may partly explain the health benefits of nut consumption.
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Affiliation(s)
- Rosa M. Lamuel-Raventos
- Department of Nutrition and Food Science-XARTA-INSA, School of Pharmacy, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Marie-Pierre St. Onge
- Department of Medicine and Institute of Human Nutrition, Columbia University, New York, New York, USA
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22
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Karthi N, Karthiga A, Kalaiyarasu T, Stalin A, Manju V, Singh SK, Cyril R, Lee SM. Exploration of cell cycle regulation and modulation of the DNA methylation mechanism of pelargonidin: Insights from the molecular modeling approach. Comput Biol Chem 2017; 70:175-185. [PMID: 28950208 DOI: 10.1016/j.compbiolchem.2017.08.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 03/28/2017] [Accepted: 08/01/2017] [Indexed: 12/18/2022]
Abstract
Pelargonidin is an anthocyanidin isolated from plant resources. It shows strong cytotoxicity toward various cancer cell lines, even though the carcinogenesis-modulating pathway of pelargonidin is not yet known. One of our previous reports showed that pelargonidin arrests the cell cycle and induces apoptosis in HT29 cells. Flowcytometry and immunoblot analysis confirmed that pelargonidin specifically inhibits the activation of CDK1 and blocks the G2-M transition of the cell cycle. In addition, DNA fragmentation was observed along with induction of cytochrome c release-mediated apoptosis. Hence, the aim of the present study was to investigate the molecular mechanism of pelargonidin's action on cell cycle regulators CDK1, CDK4, and CDK6 as well as the substrate-binding domain of DNMT1 and DNMT3A, which regulate the epigenetic signals related to DNA methylation. The results of docking analysis, binding free energy calculation, and molecular dynamics simulation correlated with the experimental results, and pelargonidin showed a specific interaction with CDK1. In this context, pelargonidin may also inhibit the recognition of DNA and catalytic binding by DNMT1 and DNMT3A. The HOMO-LUMO analysis mapped the functional groups of pelargonidin. Prediction of pharmacological descriptors suggested that pelargonidin can serve as a multitarget inhibitor for cancer treatment.
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Affiliation(s)
- Natesan Karthi
- Department of Biochemistry, Periyar University, Salem 636011, Tamilnadu, India; Division of Biotechnology, Advanced Institute of Environment and Bioscience, Safety, Environment and Life Science Institute, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan 54596, South Korea
| | | | | | - Antony Stalin
- Center for Advanced Studies (CAS) in Botany, University of Madras, Guindy Campus, Chennai - 600 025. India
| | - Vaiyapuri Manju
- Department of Biochemistry, Periyar University, Salem 636011, Tamilnadu, India.
| | - Sanjeev Kumar Singh
- Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi 630 003, Tamil Nadu, India
| | - Ravi Cyril
- Department of Zoology, Thiagarajar College, Madurai 625009, Tamilnadu, India
| | - Sang-Myeong Lee
- Division of Biotechnology, Advanced Institute of Environment and Bioscience, Safety, Environment and Life Science Institute, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan 54596, South Korea.
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23
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Toscano LT, Silva AS, Toscano LT, Tavares RL, Biasoto ACT, de Camargo AC, da Silva CSO, Gonçalves MDCR, Shahidi F. Phenolics from purple grape juice increase serum antioxidant status and improve lipid profile and blood pressure in healthy adults under intense physical training. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.03.063] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Hinojosa-Nogueira D, Muros J, Rufián-Henares JA, Pastoriza S. New Method To Estimate Total Polyphenol Excretion: Comparison of Fast Blue BB versus Folin-Ciocalteu Performance in Urine. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2017; 65:4216-4222. [PMID: 28474524 DOI: 10.1021/acs.jafc.7b01000] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Polyphenols are bioactive substances of vegetal origin with a significant impact on human health. The assessment of polyphenol intake and excretion is therefore important. The Folin-Ciocalteu (F-C) method is the reference assay to measure polyphenols in foods as well as their excretion in urine. However, many substances can influence the method, making it necessary to conduct a prior cleanup using solid-phase extraction (SPE) cartridges. In this paper, we demonstrate the use of the Fast Blue BB reagent (FBBB) as a new tool to measure the excretion of polyphenols in urine. Contrary to F-C, FBBB showed no interference in urine, negating the time-consuming and costly SPE cleanup. In addition, it showed excellent linearity (r2 = 0.9997), with a recovery of 96.4% and a precision of 1.86-2.11%. The FBBB method was validated to measure the excretion of polyphenols in spot urine samples from Spanish children, showing a good correlation between polyphenol intake and excretion.
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Affiliation(s)
- Daniel Hinojosa-Nogueira
- Departamento de Nutrición y Bromatología, Facultad de Farmacia and ‡Instituto de Investigación Biosanitaria (ibs.GRANADA), Universidad de Granada , Campus Universitario de Cartuja, 18071 Granada, Spain
| | - Joaquín Muros
- Departamento de Nutrición y Bromatología, Facultad de Farmacia and ‡Instituto de Investigación Biosanitaria (ibs.GRANADA), Universidad de Granada , Campus Universitario de Cartuja, 18071 Granada, Spain
| | - José A Rufián-Henares
- Departamento de Nutrición y Bromatología, Facultad de Farmacia and ‡Instituto de Investigación Biosanitaria (ibs.GRANADA), Universidad de Granada , Campus Universitario de Cartuja, 18071 Granada, Spain
| | - Silvia Pastoriza
- Departamento de Nutrición y Bromatología, Facultad de Farmacia and ‡Instituto de Investigación Biosanitaria (ibs.GRANADA), Universidad de Granada , Campus Universitario de Cartuja, 18071 Granada, Spain
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Plumb J, Pigat S, Bompola F, Cushen M, Pinchen H, Nørby E, Astley S, Lyons J, Kiely M, Finglas P. eBASIS (Bioactive Substances in Food Information Systems) and Bioactive Intakes: Major Updates of the Bioactive Compound Composition and Beneficial Bioeffects Database and the Development of a Probabilistic Model to Assess Intakes in Europe. Nutrients 2017; 9:nu9040320. [PMID: 28333085 PMCID: PMC5409659 DOI: 10.3390/nu9040320] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 03/09/2017] [Accepted: 03/17/2017] [Indexed: 01/15/2023] Open
Abstract
eBASIS (Bioactive Substances in Food Information Systems), a web-based database that contains compositional and biological effects data for bioactive compounds of plant origin, has been updated with new data on fruits and vegetables, wheat and, due to some evidence of potential beneficial effects, extended to include meat bioactives. eBASIS remains one of only a handful of comprehensive and searchable databases, with up-to-date coherent and validated scientific information on the composition of food bioactives and their putative health benefits. The database has a user-friendly, efficient, and flexible interface facilitating use by both the scientific community and food industry. Overall, eBASIS contains data for 267 foods, covering the composition of 794 bioactive compounds, from 1147 quality-evaluated peer-reviewed publications, together with information from 567 publications describing beneficial bioeffect studies carried out in humans. This paper highlights recent updates and expansion of eBASIS and the newly-developed link to a probabilistic intake model, allowing exposure assessment of dietary bioactive compounds to be estimated and modelled in human populations when used in conjunction with national food consumption data. This new tool could assist small- and medium-sized enterprises (SMEs) in the development of food product health claim dossiers for submission to the European Food Safety Authority (EFSA).
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Affiliation(s)
- Jenny Plumb
- Institute of Food Research, Norwich NR4 7UA, UK.
| | | | | | - Maeve Cushen
- Creme Global, Grand Canal Quay, Dublin 2, Ireland.
| | | | - Eric Nørby
- Polytec ApS, Niva, 2990 Copenhagen, Denmark.
| | - Siân Astley
- EuroFIR Association Internationale Sans But Lucratif, 40, Rue Washington, 1050 Brussels, Belgium.
| | - Jacqueline Lyons
- School of Food and Nutritional Sciences, University College Cork, T12 Y337 Cork, Ireland.
| | - Mairead Kiely
- School of Food and Nutritional Sciences, University College Cork, T12 Y337 Cork, Ireland.
| | - Paul Finglas
- Institute of Food Research, Norwich NR4 7UA, UK.
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Cires MJ, Wong X, Carrasco-Pozo C, Gotteland M. The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins. Front Nutr 2017; 3:57. [PMID: 28097121 PMCID: PMC5206694 DOI: 10.3389/fnut.2016.00057] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Accepted: 12/13/2016] [Indexed: 12/11/2022] Open
Abstract
Proanthocyanidins (PACs) are polymers of flavan-3-ols abundant in many vegetable foods and beverages widely consumed in the human diet. There is increasing evidence supporting the beneficial impact of dietary PACs in the prevention and nutritional management of non-communicable chronic diseases. It is considered that PACs with a degree of polymerization >3 remain unabsorbed in the gastrointestinal (GI) tract and accumulate in the colonic lumen. Accordingly, the GI tract may be considered as a key organ for the healthy-promoting effects of dietary PACs. PACs form non-specific complexes with salivary proteins in mouth, originating the sensation of astringency, and with dietary proteins, pancreatic enzymes, and nutrient transporters in the intestinal lumen, decreasing the digestion and absorption of carbohydrates, proteins, and lipids. They also exert antimicrobial activities, interfering with cariogenic or ulcerogenic pathogens in the mouth (Streptococcus mutans) and stomach (Helicobacter pylori), respectively. Through their antioxidant and antiinflammatory properties, PACs decrease inflammatory processes in animal model of gastric and colonic inflammation. Interestingly, they exert prebiotic activities, stimulating the growth of Lactobacillus spp. and Bifidobacterium spp. as well as some butyrate-producing bacteria in the colon. Finally, PACs are also metabolized by the gut microbiota, producing metabolites, mainly aromatic acids and valerolactones, which accumulate in the colon and/or are absorbed into the bloodstream. Accordingly, these compounds could display biological activities on the colonic epithelium or in extra-intestinal tissues and, therefore, contribute to part of the beneficial effects of dietary PACs.
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Affiliation(s)
- María José Cires
- Faculty of Medicine, Department of Nutrition, University of Chile , Santiago , Chile
| | - Ximena Wong
- Faculty of Medicine, Department of Nutrition, University of Chile , Santiago , Chile
| | | | - Martin Gotteland
- Faculty of Medicine, Department of Nutrition, University of Chile, Santiago, Chile; Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile
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Rosato V, Guercio V, Bosetti C, Negri E, Serraino D, Giacosa A, Montella M, La Vecchia C, Tavani A. Mediterranean diet and colorectal cancer risk: a pooled analysis of three Italian case-control studies. Br J Cancer 2016; 115:862-5. [PMID: 27537381 PMCID: PMC5046203 DOI: 10.1038/bjc.2016.245] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 07/11/2016] [Accepted: 07/18/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Adherence to the Mediterranean diet (MD) is associated with a reduced risk of several cancers. However, studies conducted in Mediterranean regions are scanty. METHODS To investigate the relation between MD and colorectal cancer risk in Italy, we pooled data from three case-control studies, including a total of 3745 colorectal cancer cases and 6804 hospital controls. Adherence to the MD was assessed using an a priori Mediterranean Diet Score (MDS), based on nine components. RESULTS Compared with the lowest adherence to the MD (0-2 MDS), the odds ratio (OR) was 0.52 (95% confidence interval (CI) 0.43-0.62) for the highest adherence (7-9 MDS), with a significant inverse trend in risk (P<0.0001). The OR for a 1-point increment in the MDS was 0.89 (95% CI 0.86-0.91). The inverse association was consistent across studies, cancer anatomical subsites and strata of selected covariates. CONCLUSIONS This Italian study confirms a favourable role of MD on colorectal cancer risk.
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Affiliation(s)
- Valentina Rosato
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.,Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Valentina Guercio
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Cristina Bosetti
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy
| | - Eva Negri
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy
| | - Diego Serraino
- Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico Aviano IRCCS, Aviano, Italy
| | - Attilio Giacosa
- Department of Gastroenterology and Clinical Nutrition, Policlinico di Monza, Monza, Italy
| | - Maurizio Montella
- Epidemiology Unit, National Cancer Institute, 'G. Pascale' Foundation, Naples, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Alessandra Tavani
- Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy
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Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer. Diseases 2016; 4:diseases4010006. [PMID: 28933386 PMCID: PMC5456306 DOI: 10.3390/diseases4010006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 01/14/2016] [Accepted: 01/15/2016] [Indexed: 01/22/2023] Open
Abstract
Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated.
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Choy YY, Fraga M, Mackenzie GG, Waterhouse AL, Cremonini E, Oteiza PI. The PI3K/Akt pathway is involved in procyanidin‐mediated suppression of human colorectal cancer cell growth. Mol Carcinog 2016; 55:2196-2209. [DOI: 10.1002/mc.22461] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 01/04/2016] [Accepted: 01/06/2016] [Indexed: 12/13/2022]
Affiliation(s)
- Ying Yng Choy
- Department of Viticulture and EnologyUniversity of CaliforniaDavisCalifornia
| | - Magdalena Fraga
- Departments of Nutrition and Environmental ToxicologyUniversity of CaliforniaDavisCalifornia
| | - Gerardo G. Mackenzie
- Department of Preventive MedicineStony Brook Cancer CenterStony Brook UniversityStony BrookNew York
| | | | - Eleonora Cremonini
- Departments of Nutrition and Environmental ToxicologyUniversity of CaliforniaDavisCalifornia
| | - Patricia I. Oteiza
- Departments of Nutrition and Environmental ToxicologyUniversity of CaliforniaDavisCalifornia
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Temraz S, Alameddine R, Shamseddine A. Angioprevention in Colon Cancer from Bench to Bedside. CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0300-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
High intakes of fruit and vegetables may reduce the risk of cancer at several sites. Evidence has been derived mainly from case-control studies. We reviewed the relationship between consumption of vegetables and fruit and the risk of several common cancers in a network of Italian and Swiss case-control studies including over 10,000 cases of fourteen different cancers and about 17,000 controls. Data were suggestive of a protective role of vegetable intake on the risk of several common epithelial cancers. OR for the highest compared with the lowest levels of consumption ranged from 0.2 (larynx, oral cavity and pharynx) to 0.9 (prostate). Inverse associations were found for both raw and cooked vegetables, although for upper digestive tract cancers the former were somewhat stronger. Similar inverse associations were found for cruciferous vegetables. Frequent consumption of allium vegetables was also associated with reduced risk of several cancers. Fruit was a favourable correlate of the risk of several cancers, particularly of the upper digestive tract, with associations generally weaker than those reported for vegetables. A reduced risk of cancers of the digestive tract and larynx was found for high consumption of citrus fruit. Suggestive protections against several forms of cancer, mainly digestive tract cancers, were found for high consumption of apples and tomatoes. High intakes of fibres, flavonoids and proanthocyanidins were inversely related to various forms of cancer. In conclusion, data from our series of case-control studies suggested a favourable role of high intakes of fruit and vegetables in the risk of many common cancers, particularly of the digestive tract. This adds evidence to the indication that aspects of the Mediterranean diet may have a favourable impact not only on CVD, but also on several common (epithelial) cancers, particularly of the digestive tract.
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Abstract
Diet and inflammation have been suggested to be important risk factors for colorectal cancer (CRC). In the present study, we examined the association between the dietary inflammatory index (DII) and the risk of CRC in a multi-centre case-control study conducted between 1992 and 1996 in Italy. The study included 1225 incident colon cancer cases, 728 incident rectal cancer cases and 4154 controls hospitalised for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed using a validated seventy-eight-item FFQ that included assessment of alcohol intake. Logistic regression models were used to estimate the OR adjusted for age, sex, study centre, education, BMI, alcohol drinking, physical activity and family history of CRC. Energy intake was adjusted using the residual method. Subjects with higher DII scores (i.e. with a more pro-inflammatory diet) had a higher risk of CRC, with the DII being used both as a continuous variable (OR(continuous) 1.13, 95 % CI 1.09, 1.18) and as a categorical variable (OR(quintile 5 v. 1) 1.55, 95 % CI 1.29, 1.85; P for trend < 0.0001). Similar results were observed when the analyses were carried out separately for colon and rectal cancer cases. These results indicate that a pro-inflammatory diet is associated with an increased risk of CRC.
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Olaku OO, Ojukwu MO, Zia FZ, White JD. The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies. Nutr Cancer 2015; 67:730-40. [PMID: 25880972 DOI: 10.1080/01635581.2015.1029639] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced by chemotherapy. Doxorubicin was the most common chemotherapeutic drug studied followed by cisplatin. Research studies that assessed the effect of GSE or GSP on radiation treatment accounted for 22% of the articles reviewed. GSE/GSP ameliorates some of the cytotoxic effects on normal cells/tissues induced by chemo/radiotherapy.
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Affiliation(s)
- Oluwadamilola O Olaku
- a Office of Cancer Complementary and Alternative Medicine, National Cancer Institute , Bethesda , Maryland , USA and Kelly Services , Rockville , Maryland , USA
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Verstraeten SV, Fraga CG, Oteiza PI. Interactions of flavan-3-ols and procyanidins with membranes: mechanisms and the physiological relevance. Food Funct 2014; 6:32-41. [PMID: 25418533 DOI: 10.1039/c4fo00647j] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Flavonoids are a type of phenolic compound widely present in edible plants. A great number of health benefits have been ascribed to flavonoid consumption in the human population. However, the molecular mechanisms involved in such effects remain to be identified. The flavan-3-ols (-)-epicatechin and (+)-catechin, and their related oligomers (procyanidins) have been thoroughly studied because of their capacity to interact with cell membranes. Starting with these interactions, procyanidins could modulate multiple biochemical processes, such as enzyme activities, receptor-ligand binding, membrane-initiated cell signaling, and molecule transport across membranes. This review focuses on molecular aspects of procyanidin interactions with membrane lipid components, and the resulting protection of the membranes against mechanical and/or oxidative damage, resulting in the maintenance of cell functions.
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Affiliation(s)
- Sandra V Verstraeten
- Department of Biological Chemistry and IQUIFIB (UBA-CONICET), Buenos Aires, Argentina
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35
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de Camargo AC, Vidal CMM, Canniatti-Brazaca SG, Shahidi F. Fortification of cookies with peanut skins: effects on the composition, polyphenols, antioxidant properties, and sensory quality. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:11228-11235. [PMID: 25350915 DOI: 10.1021/jf503625p] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Food fortification may be carried out to improve the health status of consumers. In this study, peanut skins were added at 1.3, 1.8, and 2.5% to cookies to increase their polyphenol content. Insoluble fiber was increased by up to 52%. In addition, total phenolic content and the corresponding antioxidant capacities also increased as evidenced by increases of epicatechin and procyanidin dimers A and B. In addition, trimers and tetramers of procyanidins were identified only in peanut skin-fortified cookies. Addition of 2.5% peanut skins rendered an increase of up to 30% in the total polyphenols as evaluated by high-performance liquid chromatography-diode array detection-electrospray ionization multistage mass spectrometry (HPLC-DAD-ESI-MS(n)). Sensory evaluation results demonstrated that peanut skin-fortified cookies were well accepted, which suggests that the present formulation may lend itself for commercial exploitation.
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Affiliation(s)
- Adriano Costa de Camargo
- Department of Biochemistry, Memorial University of Newfoundland , St. John's, NL, Canada A1B 3X9
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36
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Feng LL, Liu BX, Zhong JY, Sun LB, Yu HS. Effect of grape procyanidins on tumor angiogenesis in liver cancer xenograft models. Asian Pac J Cancer Prev 2014; 15:737-41. [PMID: 24568488 DOI: 10.7314/apjcp.2014.15.2.737] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. METHODS A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. RESULTS The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. CONCLUSIONS These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.
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Affiliation(s)
- Li-Li Feng
- Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, China E-mail :
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Chen Q, Liu XF, Zheng PS. Grape seed proanthocyanidins (GSPs) inhibit the growth of cervical cancer by inducing apoptosis mediated by the mitochondrial pathway. PLoS One 2014; 9:e107045. [PMID: 25187959 PMCID: PMC4154836 DOI: 10.1371/journal.pone.0107045] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 08/04/2014] [Indexed: 11/30/2022] Open
Abstract
Grape seed proanthocyanidins (GSPs), a biologically active component of grape seeds, have been reported to possess a wide array of pharmacological and biochemical properties. Recently, the inhibitory effects of GSPs on various cancers have been reported, but their effects on cervical cancer remain unclear. Here, we explored the effect of GSPs on cervical cancer using in vitro and in vivo models. In vitro, the treatment of HeLa and SiHa cells with GSPs resulted in a significant inhibition of cell viability. Further investigation indicated that GSPs led to the dose-dependent induction of apoptosis in cancer cells. The underlying mechanism was associated with increased expression of the pro-apoptotic protein Bak-1, decreased expression of the anti-apoptotic protein Bcl-2, the loss of mitochondrial membrane potential, and the activation of caspase-3, suggesting that GSPs induced cervical cancer cell apoptosis through the mitochondrial pathway. In addition, the administration of GSPs (0.1%, 0.2%, and 0.4%, w/v) as a supplement in drinking water significantly inhibited the tumor growth of HeLa and SiHa cells in athymic nude mice, and the number of apoptotic cells in those tumors was also increased significantly. Taken together, our studies demonstrated that GSPs could inhibit the growth of cervical cancer by inducing apoptosis through the mitochondrial pathway, which provides evidence indicating that GSPs may be a potential chemopreventive and/or chemotherapeutic agent for cervical cancer.
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Affiliation(s)
- Qing Chen
- The Department of Reproductive Medicine, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China
- The Department of Biochemistry and Molecular Biology, Medical College of Xi’an Jiaotong University, Xi’an, China
| | - Xiao-Fang Liu
- The Department of Reproductive Medicine, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China
- The Department of Pharmacology, Medical College of Xi’an Jiaotong University, Xi’an, China
| | - Peng-Sheng Zheng
- The Department of Reproductive Medicine, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China
- The Department of Biochemistry and Molecular Biology, Medical College of Xi’an Jiaotong University, Xi’an, China
- The Section of Cancer Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People’s Republic of China, Xi’an, China
- * E-mail:
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Verstraeten SV, Jaggers GK, Fraga CG, Oteiza PI. Procyanidins can interact with Caco-2 cell membrane lipid rafts: Involvement of cholesterol. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2013; 1828:2646-53. [DOI: 10.1016/j.bbamem.2013.07.023] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 07/12/2013] [Accepted: 07/16/2013] [Indexed: 11/28/2022]
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La Vecchia C, Decarli A, Serafini M, Parpinel M, Bellocco R, Galeone C, Bosetti C, Zucchetto A, Polesel J, Lagiou P, Negri E, Rossi M. Dietary total antioxidant capacity and colorectal cancer: A large case-control study in Italy. Int J Cancer 2013; 133:1447-51. [DOI: 10.1002/ijc.28133] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Accepted: 02/07/2013] [Indexed: 12/22/2022]
Affiliation(s)
| | | | - Mauro Serafini
- Agricultural Research Council; CRA Ex-INRAN; Rome; Italy
| | - Maria Parpinel
- Unit of Hygiene and Epidemiology; Department of Biological and Medical Sciences, University of Udine; Udine; Italy
| | | | | | - Cristina Bosetti
- Department of Epidemiology; Istituto di Ricerche Farmacologiche Mario Negri-IRCCS; Milan; Italy
| | | | - Jerry Polesel
- Unit of Epidemiology and Biostatistics; Centro di Riferimento Oncologico; Aviano; Italy
| | | | - Eva Negri
- Department of Epidemiology; Istituto di Ricerche Farmacologiche Mario Negri-IRCCS; Milan; Italy
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Woo HD, Kim J. Dietary flavonoid intake and risk of stomach and colorectal cancer. World J Gastroenterol 2013; 19:1011-1019. [PMID: 23467443 PMCID: PMC3581988 DOI: 10.3748/wjg.v19.i7.1011] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Accepted: 02/06/2013] [Indexed: 02/06/2023] Open
Abstract
Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.
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Choy YY, Jaggers GK, Oteiza PI, Waterhouse AL. Bioavailability of intact proanthocyanidins in the rat colon after ingestion of grape seed extract. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2013; 61:121-127. [PMID: 23244439 DOI: 10.1021/jf301939e] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Current evidence shows that monomeric flavonoids are known to be only slightly absorbed in the small intestine, but the metabolism of oligomeric and polymeric proanthocyanidins (PAC) in the colon is poorly understood. The objective of this study was to optimize the analysis of grape seed extract (GSE) in feces and use that method to assess the presence of PAC in the colon after ingestion of GSE. Rats were fed a diet ad libitum containing 0.25% (w/w) GSE for 10 days. Feces were collected daily and colonic contents at sacrifice on day 10, respectively. The recovery of fecal PAC using a solid-phase extraction (SPE) method was >70%. PAC were separated by normal-phase HPLC with fluorescence detection, and subsequent peak confirmation was done by MS-ion trap. The concentration of colonic contents at day 10 was 13.9 mg/kg for monomer, and those for oligomers (dimers-hexamers) were 33.4, 84.6, 87.2, 57.3, and 35.7 mg/kg, respectively. The concentration of monomeric and oligomeric PAC in daily feces was similar among days. In the mass balance analysis, approximately 11% of ingested PAC was recovered in the feces. These findings indicate that ingested PAC were present in the colon as the intact parent compounds and thus may contribute to the health of the gastrointestinal tract.
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Affiliation(s)
- Ying Yng Choy
- Department of Viticulture and Enology, University of California, Davis, California 95616, United States
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Huang S, Yang N, Liu Y, Gao J, Huang T, Hu L, Zhao J, Li Y, Li C, Zhang X. Grape seed proanthocyanidins inhibit colon cancer-induced angiogenesis through suppressing the expression of VEGF and Ang1. Int J Mol Med 2012; 30:1410-6. [PMID: 23026853 DOI: 10.3892/ijmm.2012.1147] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2012] [Accepted: 09/04/2012] [Indexed: 11/06/2022] Open
Abstract
Tumor cells trigger angiogenesis through overexpression of various angiogenic factors including vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). Therefore, inhibition of the expression of both VEGF and Ang1, the initial step of tumor angiogenesis, is a promising strategy for cancer chemoprevention and therapy. Grape seed proanthocyanidins (GSPs) are widely consumed dietary supplements that have antitumor activity. Due to their polymeric structure, GSPs are poorly absorbed along the gastrointestinal tract and can reach the colon at high concentrations, allowing these chemicals to act as chemopreventive agents for colon cancer. In the present study, we found that GSPs inhibited colon tumor-induced angiogenesis and, thus, the growth of colon tumor xenografts on the chick chorioallantoic membranes. The mechanisms of their action were related to inhibiting the expression of both VEGF and Ang1 through scavenging reactive oxygen species. Previous studies have demonstrated that the chemopreventive effects of GSPs on colon cancer are associated with their growth inhibitory and apoptosis-inducing effects. Our results demonstrate another mechanism by which GSPs inhibit colon tumor growth, which will be helpful for developing GSPs as a pharmacologically safe angiopreventive agent against colorectal cancer.
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Affiliation(s)
- Shuangsheng Huang
- Medical College of Northwest University for Nationalities, Lanzhou, Gansu, P.R. China.
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Association between habitual dietary flavonoid and lignan intake and colorectal cancer in a Spanish case-control study (the Bellvitge Colorectal Cancer Study). Cancer Causes Control 2012; 24:549-57. [PMID: 22588680 DOI: 10.1007/s10552-012-9992-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2011] [Accepted: 05/04/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Flavonoid-rich foods, such as fruits, vegetables, and tea, may have a protective effect upon colorectal cancer. However, current epidemiological evidence for a protective effect of flavonoid intake upon colorectal cancer is promising but not conclusive. OBJECTIVE To examine the relation between dietary flavonoid and lignan intakes and the risk of colorectal cancer within a Spanish population. DESIGN Data from the Bellvitge Colorectal Cancer Study, a case-control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. A reproducible and validated food frequency questionnaire was administered in personal interviews. An ad hoc food composition database on flavonoids and lignans was compiled, mainly using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using unconditional logistic regression models. RESULTS An inverse association was found between intake of total flavonoids (OR, 0.59; 95 % CI, 0.35-0.99 for the highest vs. the lowest quartile; p for trend = 0.04), lignans (OR, 0.59; 95 % CI, 0.34-0.99; p for trend = 0.03), and some individual flavonoid subgroups (flavones, proanthocyanidins) and the risk of colorectal cancer. Separate analyses by cancer site showed similar results. CONCLUSIONS Intake of total dietary flavonoids (particularly certain flavonoid subgroups) and lignans was inversely associated with colorectal cancer risk in a Spanish population.
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Bobe G, Murphy G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Cross AJ. Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial. Int J Cancer 2012; 130:1649-59. [PMID: 21618513 PMCID: PMC3235262 DOI: 10.1002/ijc.26184] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Accepted: 04/21/2011] [Indexed: 12/17/2022]
Abstract
Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest vs. lowest lignan intake quartile OR = 2.07, 95% CI: 1.22-3.52, p trend = 0.004) but not in men (p interaction = 0.04). To conclude, dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women.
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Affiliation(s)
- Gerd Bobe
- Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Frederick, MD, USA.
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Antiproliferative and apoptotic effects triggered by Grape Seed Extract (GSE) versus epigallocatechin and procyanidins on colon cancer cell lines. Int J Mol Sci 2012; 13:651-664. [PMID: 22312277 PMCID: PMC3269711 DOI: 10.3390/ijms13010651] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2011] [Revised: 11/14/2011] [Accepted: 01/04/2012] [Indexed: 01/03/2023] Open
Abstract
Grape seed extract has been proven to exert anticancer effects on different tumors. These effects are mainly ascribed to catechin and procyanidin content. Analytical studies demonstrated that grape seed extract composition is complex and it is likely other components could exert biological activities. Using cell count and flow cytometry assays, we evaluated the cytostatic and apoptotic effects produced by three different grape seed extracts from Italia, Palieri and Red Globe cultivars, on Caco2 and HCT-8 colon cancer cells. These effects were compared to those induced by epigallocatechin and procyanidins, alone or in association, on the same cell lines. All the extracts induced growth inhibition and apoptosis in Caco2 and HCT-8 cells, along the intrinsic apoptotic pathway. On both cell lines, growth inhibition induced by Italia and Palieri grape seed extracts was significantly higher than that it has been recorded with epigallocatechin, procyanidins and their association. In Caco2 cells, the extract from Red Globe cultivar was less effective in inducing growth inhibition than procyanidins alone and in association with epigallocatechin, whereas, in HCT-8 cells, only the association of epigallocatechin and procyanidins triggers a significant proliferation decrease. On both cell lines, apoptosis induced by Italia, Palieri and Red Globe grape seed extracts was considerably higher than has been recorded with epigallocatechin, procyanidins and their association. These data support the hypothesis by which other compounds, present in the grape seed extracts, are likely to enhance the anticancer effects.
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Da Silva M, Jaggers GK, Verstraeten SV, Erlejman AG, Fraga CG, Oteiza PI. Large procyanidins prevent bile-acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells. Free Radic Biol Med 2012; 52:151-9. [PMID: 22074817 DOI: 10.1016/j.freeradbiomed.2011.10.436] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2011] [Revised: 09/30/2011] [Accepted: 10/07/2011] [Indexed: 11/24/2022]
Abstract
Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water-lipid interface. Hex (2.5-20 μM) inhibited DCA-triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen-activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane-associated events can in part explain the beneficial effects of procyanidins on CRC.
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Affiliation(s)
- Mathieu Da Silva
- Department of Nutrition, University of California, Davis, CA 95616, USA
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Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr 2011; 108:1095-108. [PMID: 22186699 DOI: 10.1017/s0007114511006386] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35-74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.
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Lizarraga D, Vinardell MP, Noé V, van Delft JH, Alcarraz-Vizán G, van Breda SG, Staal Y, Günther UL, Carrigan JB, Reed MA, Ciudad CJ, Torres JL, Cascante M. A lyophilized red grape pomace containing proanthocyanidin-rich dietary fiber induces genetic and metabolic alterations in colon mucosa of female C57BL/6J mice. J Nutr 2011; 141:1597-604. [PMID: 21775529 DOI: 10.3945/jn.110.133199] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Diet plays a decisive role in promoting or preventing colon cancer. However, the specific effects of some nutrients remain unclear. The capacity of fruit and vegetables to prevent cancer has been associated with their fiber and antioxidant composition. We investigated whether consumption of a lyophilized red grape pomace containing proanthocyanidin-rich dietary fiber (grape antioxidant dietary fiber, GADF) by female C57BL/6J mice would affect the serum metabolic profile or colon mucosa gene expression using NMR techniques and DNA microarray, respectively. The mice were randomly assigned to 2 groups that for 2 wk consumed a standard rodent diet and were gavaged with 100 mg/kg body weight GADF suspended in water or an equivalent volume of plain tap water (10 mL/kg body weight). The amount of fiber supplemented was calculated to equal the current recommended daily levels of fiber consumption for humans. The inclusion of dietary GADF induced alterations in the expression of tumor suppressor genes and proto-oncogenes as well as the modulation of genes from pathways, including lipid biosynthesis, energy metabolism, cell cycle, and apoptosis. Overexpression of enzymes pertaining to the xenobiotic detoxifying system and endogenous antioxidant cell defenses was also observed. In summary, the genetic and metabolic profiles induced by GADF were consistent with the preventive effects of fiber and polyphenols. On the basis of these observations, we propose that GADF may contribute to reducing the risk of colon cancer.
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Affiliation(s)
- Daneida Lizarraga
- Department of Biochemistry and Molecular Biology, Biology Faculty, Universitat de Barcelona, Biomedicine Institute from Universitat de Barcelona, and Associated Unit with CSIC (Consejo Superior de Investigaciones Científicas), Barcelona, Spain
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Fraga CG, Oteiza PI. Dietary flavonoids: Role of (-)-epicatechin and related procyanidins in cell signaling. Free Radic Biol Med 2011; 51:813-23. [PMID: 21699974 DOI: 10.1016/j.freeradbiomed.2011.06.002] [Citation(s) in RCA: 182] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2010] [Revised: 05/07/2011] [Accepted: 06/02/2011] [Indexed: 02/07/2023]
Abstract
Plant polyphenols are among the most abundant phytochemicals present in human diets. Increasing evidence supports the health-promoting effects of certain polyphenols, including flavonoids. This review discusses current knowledge of the capacity of monomeric flavanols, i.e., (-)-epicatechin and (+)-catechin, and their derived procyanidins to modulate cell signaling and the associations of these actions with better health. Flavanols and procyanidins can regulate cell signaling through different mechanisms of action. Monomers and dimeric procyanidins can be transported inside cells and directly interact and modulate the activity of signaling proteins and/or prevent oxidation. Larger and nonabsorbable procyanidins can regulate cell signaling by interacting with cell membrane proteins and lipids, inducing changes in membrane biophysics, and by modulating oxidant production. All these actions would be limited by the bioavailability of flavanols at the target tissue. The protection from cardiac and vascular disease and from cancer that is associated with a high consumption of fruit and vegetables could be in part explained by the capacity of flavanols and related procyanidins to modulate proinflammatory and oncogenic signals.
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Affiliation(s)
- Cesar G Fraga
- Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina.
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Pérez-Jiménez J, Hubert J, Hooper L, Cassidy A, Manach C, Williamson G, Scalbert A. Urinary metabolites as biomarkers of polyphenol intake in humans: a systematic review. Am J Clin Nutr 2010; 92:801-9. [PMID: 20810980 DOI: 10.3945/ajcn.2010.29924] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND To identify associations between polyphenol intake and health and disease outcomes in cohort studies, it is important to identify biomarkers of intake for the various compounds commonly consumed as part of the diet. OBJECTIVE The objective of this systematic review was to assess the usefulness of polyphenol metabolites excreted in urine as biomarkers of polyphenol intake in humans. DESIGN The method included a structured search strategy for polyphenol intervention studies on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction into an Access database; validity assessment; and meta-analysis. RESULTS One hundred sixty-two controlled intervention studies with polyphenols were included, and mean recovery yield and correlations with the dose ingested were determined for 40 polyphenols. Polyphenols such as daidzein, genistein, glycitein, enterolactone, and hydroxytyrosol showed both a high recovery yield (12-37%) and a high correlation with the dose (Pearson's correlation coefficients: 0.67-0.87), which showed good sensitivity and robustness as biomarkers of intake throughout the different studies. Weaker recovery for anthocyanins (0.06-0.2%) and weaker correlations with dose [Pearson's correlation coefficients: 0.21-0.52 for hesperidin, naringenin, (-)-epicatechin, (-)-epigallocatechin, quercetin, and 3 microbial metabolites of isoflavones (dihydrodaidzein, equol, and O-desmethylangolensin)] suggest that they are currently less suitable as biomarkers of intake. CONCLUSIONS These data confirm the value of certain urinary polyphenols as biomarkers of intake. A validation in populations is now needed to evaluate their specificity, sensitivity, and responsiveness to dose under free-living conditions.
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Affiliation(s)
- Jara Pérez-Jiménez
- Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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