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1
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Lopes P, Ferreira IMPLVO, Petronilho S, Passos CP. The road for red raspberry seeds valorization: A comprehensive review on the chemical composition, extraction techniques, bioactivity and applications. Food Chem 2025; 486:144658. [PMID: 40383065 DOI: 10.1016/j.foodchem.2025.144658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 04/30/2025] [Accepted: 05/05/2025] [Indexed: 05/20/2025]
Abstract
Raspberry seeds (RS) are rich in polysaccharides, triacylglycerides, and polyphenols, but detailed composition information remains largely scarce and centered on its specialty oil (RSO). Furthermore, defatted RS has no application and is discarded, creating environmental and economic burdens. This comprehensive review aims to compile and critically discuss existing data on RS chemical composition, extraction techniques, bioactive properties, and current applications. RS variety and harvest conditions and lack of proper analysis and quantification methodologies impact RS deep knowledge. Green extraction techniques revealed good efficiency while supporting a sustainable approach compared to conventional ones, but their industrial scale-up is underdeveloped. RS revealed several bioactivities, mainly explored in vitro, but the structure-function relationship is often missing. Current commercial exploitation of RS biocomponents is limited to cosmetics despite RS exploration for food fortification by nutritional enrichment and oil stabilization. The findings underscore the importance of further research to fully realize the potential of RS.
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Affiliation(s)
- Paloma Lopes
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; LAQV-REQUIMTE, Laboratory of Bromatology and Hydrology, Department of Chemical Sciences, Universidade do Porto - Faculdade de Farmácia, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal.
| | - Isabel M P L V O Ferreira
- LAQV-REQUIMTE, Laboratory of Bromatology and Hydrology, Department of Chemical Sciences, Universidade do Porto - Faculdade de Farmácia, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal.
| | - Sílvia Petronilho
- LAQV-REQUIMTE & CICECO, Department of Materials and Ceramic Engineering, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Cláudia P Passos
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
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Oldani M, Guzzetti L, Pioltelli E, Sala D, Panzeri D, Brioschi M, Forcella M, Fusi P. Assessment of the Nutraceutical Properties of Wild Strawberry (Fragaria vesca L.) Extracts on Human Colorectal Cell Lines. Mol Nutr Food Res 2025:e70018. [PMID: 40207736 DOI: 10.1002/mnfr.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/20/2025] [Accepted: 02/21/2025] [Indexed: 04/11/2025]
Abstract
Colorectal cancer is the third most common cancer worldwide; its higher incidence in the Western world, compared to rural areas of Africa and Asia, led to its classification among the so-called Westernized diseases. The wild strawberry Fragaria vesca L. is endowed with several bioactive components, such as polyphenols, vitamins, terpenes, and organic acids that can contribute to cancer prevention. In this study, we chemically characterized a wild strawberry extract through high-resolution mass spectrometry and evaluated its antioxidant properties on two human colorectal cancer cell lines: KRAS mutated SW480 cells and E705 cells. We found that treatment with the extract induced cell cycle arrest in the G2 phase in SW480 cells, while it led E705 cells to apoptosis through a significant increase in the reactive oxygen species level. Wild strawberry extract is a promising dietary supplement for both wild-type and KRAS-mutated patients who exhibit a more aggressive cancer phenotype. In addition, the lack of toxicity of wild strawberry extract toward healthy colorectal cells makes this food a promising chemopreventive nutritional supplement.
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Affiliation(s)
- Monica Oldani
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Lorenzo Guzzetti
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Emiliano Pioltelli
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Davide Sala
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Davide Panzeri
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Maura Brioschi
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Matilde Forcella
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Paola Fusi
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
- Integrated Models for Prevention and Protection in Environmental and Occupational Health, (MISTRAL), Interuniversity Research Center, Italy
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El-Wetidy MS, Rady MI, Rady I, Helal H. Urolithin A affects cellular migration and modulates matrix metalloproteinase expression in colorectal cancer cells. Cell Biochem Funct 2024; 42:e4019. [PMID: 38622949 DOI: 10.1002/cbf.4019] [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: 01/24/2024] [Revised: 04/03/2024] [Accepted: 04/05/2024] [Indexed: 04/17/2024]
Abstract
Colorectal cancer (CRC) is the world's second most common gastrointestinal malignancy. Preventing tumor cell proliferation and dissemination is critical for patient survival. Polyphenols have a variety of health advantages and can help prevent cancer. The current study examined different cellular activities of the gut-microbiota metabolite urolithin A (UA) on several colon cancer cell lines. The results revealed that UA suppressed cell growth in a dose- and time-dependent manner. In the current investigation, UA substantially affected cell migration in the wound-healing experiment and greatly decreased the number of colonies generated in each CRC cell culture. UA decreased cellular migration in CRC cells 48 h after treatment, which was significant (p < .001) compared to the migration rate in untreated cells. When compared to untreated cells, UA slowed the process of colony formation by reducing the number of colonies or altering their morphological shape. The western blot analysis investigation revealed that UA inhibits cellular metastasis by lowering the expression levels of matrix metalloproteinases 1 and 2 (MMP1 and MMP2) by more than 43% and 41% (p < .001) in HT29, 28% and 149% (p < .001) in SW480, and 90% and 74% (p < .001) in SW620, respectively, at a 100 µM dosage of UA compared to the control. Surprisingly, at a 100 µM dosage of UA, the expression levels of the tissue inhibitor of metalloproteinases 1 (TIMP1) were elevated in HT29, SW480, and SW620 cells treated with 100 µM of UA by more than 89%, 57%, and 29%, respectively. Our findings imply that UA has anticancer properties and might be used therapeutically to treat CRC. The findings provided the first indication of the influence of UA on cellular migration and metastasis in colon cancer cells. All of these data showed that UA might be used as an adjuvant therapy in the treatment of various forms of CRC.
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Affiliation(s)
- Mohammad S El-Wetidy
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
- College of Medicine Research Center, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Mohamad I Rady
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
| | - Islam Rady
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
- Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Hamed Helal
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
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Wang G, Su H, Guo Z, Li H, Jiang Z, Cao Y, Li C. Rubus Occidentalis and its bioactive compounds against cancer: From molecular mechanisms to translational advances. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 126:155029. [PMID: 38417241 DOI: 10.1016/j.phymed.2023.155029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 07/05/2023] [Accepted: 08/15/2023] [Indexed: 03/01/2024]
Abstract
BACKGROUND Cancer ranks as the second leading cause of death globally, imposing a significant public health burden. The rise in cancer resistance to current therapeutic agents underscores the potential role of phytotherapy. Black raspberry (BRB, Rubus Occidentalis) is a fruit rich in anthocyanins, ellagic acid, and ellagitannins. Accumulating evidence suggests that BRB exhibits promising anticancer effects, positioning it as a viable candidate for phytotherapy. PURPOSE This article aims to review the existing research on BRB regarding its role in cancer prevention and treatment. It further analyzes the effective components of BRB, their metabolic pathways, and the potential mechanisms underlying the fruit's anticancer effects. METHODS Ovid MEDLINE, EMBASE, Web of Science, and CENTRAL were searched through the terms of Black Raspberry, Raspberry, and Rubus Occidentali up to January 2023. Two reviewers performed the study selection by screening the title and abstract. Full texts of potentially eligible studies were retrieved to access the details. RESULTS Out of the 767 articles assessed, 73 papers met the inclusion criteria. Among them, 63 papers investigated the anticancer mechanisms, while 10 conducted clinical trials focusing on cancer treatment or prevention. BRB was found to influence multiple cancer hallmarks by targeting various pathways. Decomposition of free radicals and regulation of estrogen metabolism, BRB can reduce DNA damage caused by reactive oxygen species. BRB can also enhance the function of nucleotide excision repair to repair DNA lesions. Through regulation of epigenetics, BRB can enhance the expression of tumor suppressor genes, inducing cell cycle arrest, and promoting apoptosis and pyroptosis. BRB can reduce the energy and nutrients supply to the cancer nest by inhibiting glycolysis and reducing angiogenesis. The immune and inflammatory microenvironment surrounding cancer cells can also be ameliorated by BRB, inhibiting cancer initiation and progression. However, the limited bioavailability of BRB diminishes its anticancer efficacy. Notably, topical applications of BRB, such as gels and suppositories, have demonstrated significant clinical benefits. CONCLUSION BRB inhibits cancer initiation, progression, and metastasis through diverse anticancer mechanisms while exhibiting minimal side effects. Given its potential, BRB emerges as a promising phototherapeutic agent for cancer treatment.
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Affiliation(s)
- Guanru Wang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China
| | - Hengpei Su
- College of Materials Science and Engineering, Sichuan University, No.29, Jiuyanqiao Wangjiang Rd., Chengdu 610064, China
| | - Zijian Guo
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China
| | - Honglin Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China
| | - Zhishen Jiang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China
| | - Yubin Cao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China.
| | - Chunjie Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd., Chengdu 610041, China.
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Zhao J, Li G, Ren Y, Zhang Z, Chen H, Zhang H, Zhao X, Li W, Jia Y, Guan X, Liu M. Ellagic acid inhibits human colon cancer HCT-116 cells by regulating long noncoding RNAs. Anticancer Drugs 2023; 34:1112-1121. [PMID: 36847079 PMCID: PMC10569677 DOI: 10.1097/cad.0000000000001513] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/18/2023] [Indexed: 03/01/2023]
Abstract
The natural phenolic compound ellagic acid exerts anti-cancer effects, including activity against colorectal cancer (CRC). Previously, we reported that ellagic acid can inhibit the proliferation of CRC, and can induce cell cycle arrest and apoptosis. This study investigated ellagic acid-mediated anticancer effects using the human colon cancer HCT-116 cell line. After 72 h of ellagic acid treatment, a total of 206 long noncoding RNAs (lncRNAs) with differential expression greater than 1.5-fold were identified (115 down-regulated and 91 up-regulated). Furthermore, the co-expression network analysis of differentially expressed lncRNA and mRNA showed that differential expressed lncRNA might be the target of ellagic acid activity in inhibiting CRC.
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Affiliation(s)
- Jinlu Zhao
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Guodong Li
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Yi Ren
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Zhicheng Zhang
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Hongsheng Chen
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Haopeng Zhang
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Xingyu Zhao
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Wang Li
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Yucheng Jia
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Xue Guan
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
| | - Ming Liu
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China
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A Review on Berry Seeds—A Special Emphasis on Their Chemical Content and Health-Promoting Properties. Nutrients 2023; 15:nu15061422. [PMID: 36986152 PMCID: PMC10058722 DOI: 10.3390/nu15061422] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/11/2023] [Accepted: 03/13/2023] [Indexed: 03/18/2023] Open
Abstract
Berries are important components of the human diet, valued for their high content of nutrients and active compounds. Berry seeds are also important objects of scientific investigation as, in some cases, they can have a higher concentration of certain phytochemicals than other parts of the fruit. Moreover, they are often byproducts of the food industry that can be reused to make oil, extracts, or flour. We have reviewed available literature related to the chemical content and biological activity of seeds from five different berry species—red raspberry (Rubus idaeus L. and Rubus coreanus Miq.), strawberry (Fragaria x ananassa), grape (Vitis vinifera L.), sea buckthorn (Hippophae rhamnoides L.), and cranberry (Vaccinium macrocarpon Ait.). We have searched various databases, including PubMed, Web of Knowledge, ScienceDirect, and Scopus. Last search was conducted on 16.01.2023. Various preparations from berry seeds are valuable sources of bioactive phytochemicals and could be used as functional foods or to make pharmaceuticals or cosmetics. Some products, like oil, flour, or extracts, are already available on the market. However, many preparations and compounds still lack appropriate evidence for their effectiveness in vivo, so their activity should first be assessed in animal studies and clinical trials.
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Cassotta M, Cianciosi D, De Giuseppe R, Navarro-Hortal MD, Armas Diaz Y, Forbes-Hernández TY, Pifarre KT, Pascual Barrera AE, Grosso G, Xiao J, Battino M, Giampieri F. Possible role of nutrition in the prevention of inflammatory bowel disease-related colorectal cancer: A focus on human studies. Nutrition 2023; 110:111980. [PMID: 36965240 DOI: 10.1016/j.nut.2023.111980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 01/10/2023] [Accepted: 01/22/2023] [Indexed: 02/05/2023]
Abstract
Patients with inflammatory bowel disease (IBD) are at substantially high risk for colorectal cancer (CRC). IBD-associated CRC accounts for roughly 10% to 15% of the annual mortality in patients with IBD. IBD-related CRC also affects younger patients compared with sporadic CRC, with a 5-y survival rate of 50%. Regardless of medical therapies, the persistent inflammatory state characterizing IBD raises the risk for precancerous changes and CRC, with additional input from several elements, including genetic and environmental risk factors, IBD-associated comorbidities, intestinal barrier dysfunction, and gut microbiota modifications. It is well known that nutritional habits and dietary bioactive compounds can influence IBD-associated inflammation, microbiome abundance and composition, oxidative stress balance, and gut permeability. Additionally, in recent years, results from broad epidemiologic and experimental studies have associated certain foods or nutritional patterns with the risk for colorectal neoplasia. The present study aimed to review the possible role of nutrition in preventing IBD-related CRC, focusing specifically on human studies. It emerges that nutritional interventions based on healthy, nutrient-dense dietary patterns characterized by a high intake of fiber, vegetables, fruit, ω-3 polyunsaturated fatty acids, and a low amount of animal proteins, processed foods, and alcohol, combined with probiotic supplementation have the potential of reducing IBD-activity and preventing the risk of IBD-related CRC through different mechanisms, suggesting that targeted nutritional interventions may represent a novel promising approach for the prevention and management of IBD-associated CRC.
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Affiliation(s)
- Manuela Cassotta
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
| | - Danila Cianciosi
- Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Rachele De Giuseppe
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy; NBFC, National Biodiversity Future Center, Palermo 90133, Italy
| | - Maria Dolores Navarro-Hortal
- Biomedical Research Centre, Institute of Nutrition and Food Technology "José Mataix Verdú," Department of Physiology, Faculty of Pharmacy, University of Granada, Armilla, Granada, Spain
| | - Yasmany Armas Diaz
- Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Tamara Yuliett Forbes-Hernández
- Biomedical Research Centre, Institute of Nutrition and Food Technology "José Mataix Verdú," Department of Physiology, Faculty of Pharmacy, University of Granada, Armilla, Granada, Spain
| | - Kilian Tutusaus Pifarre
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Project Department, Universidade Internacional do Cuanza, Cuito, Bié, Angola
| | - Alina Eugenia Pascual Barrera
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Department of Project Management, Universidad Internacional Iberoamericana, Campeche, Mexico
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, Universidade de Vigo - Ourense Campus, Ourense, Spain
| | - Maurizio Battino
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy; International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu University, Zhenjiang, China
| | - Francesca Giampieri
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain.
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Banc R, Rusu ME, Filip L, Popa DS. The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut-Brain Axis. Foods 2023; 12:foods12020270. [PMID: 36673365 PMCID: PMC9858309 DOI: 10.3390/foods12020270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 12/29/2022] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
Ellagitannins (ETs) are a large group of bioactive compounds found in plant-source foods, such as pomegranates, berries, and nuts. The consumption of ETs has often been associated with positive effects on many pathologies, including cardiovascular diseases, neurodegenerative syndromes, and cancer. Although multiple biological activities (antioxidant, anti-inflammatory, chemopreventive) have been discussed for ETs, their limited bioavailability prevents reaching significant concentrations in systemic circulation. Instead, urolithins, ET gut microbiota-derived metabolites, are better absorbed and could be the bioactive molecules responsible for the antioxidant and anti-inflammatory activities or anti-tumor cell progression. In this review, we examined the dietary sources, metabolism, and bioavailability of ETs, and analyzed the last recent findings on ETs, ellagic acid, and urolithins, their intestinal and brain activities, the potential mechanisms of action, and the connection between the ET microbiota metabolism and the consequences detected on the gut-brain axis. The current in vitro, in vivo, and clinical studies indicate that ET-rich foods, individual gut microbiomes, or urolithin types could modulate signaling pathways and promote beneficial health effects. A better understanding of the role of these metabolites in disease pathogenesis may assist in the prevention or treatment of pathologies targeting the gut-brain axis.
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Affiliation(s)
- Roxana Banc
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
| | - Marius Emil Rusu
- Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania
- Correspondence: ; Tel.: +40-264-450-555
| | - Lorena Filip
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
| | - Daniela-Saveta Popa
- Department of Toxicology, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
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Guo TH, Li YY, Hong SW, Cao QY, Chen H, Xu Y, Dai GL, Shao G. Evidence for Anticancer Effects of Chinese Medicine Monomers on Colorectal Cancer. Chin J Integr Med 2022; 28:939-952. [PMID: 35419728 DOI: 10.1007/s11655-022-3466-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2021] [Indexed: 12/26/2022]
Abstract
Colorectal cancer is one of the most commonly occurring cancers worldwide. Although clinical reports have indicated the anticancer effects of Chinese herbal medicine, the multiple underlying molecular and biochemical mechanisms of action remain to be fully characterized. Chinese medicine (CM) monomers, which are the active components of CM, serve as the material basis of the functional mechanisms of CM. The aim of this review is to summarize the current experimental evidence from in vitro, in vivo, and clinical studies for the effects of CM monomers in colorectal cancer prevention and treatment, providing some useful references for future research.
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Affiliation(s)
- Tian-Hao Guo
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yuan-Yuan Li
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Sheng-Wei Hong
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qian-Yu Cao
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Heng Chen
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yuan Xu
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Guo-Liang Dai
- Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
| | - Gang Shao
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
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10
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Chen P, Guo Z, Chen F, Wu Y, Zhou B. Recent Advances and Perspectives on the Health Benefits of Urolithin B, A Bioactive Natural Product Derived From Ellagitannins. Front Pharmacol 2022; 13:917266. [PMID: 35814202 PMCID: PMC9257173 DOI: 10.3389/fphar.2022.917266] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/06/2022] [Indexed: 12/11/2022] Open
Abstract
Urolithin (Uro) B is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in foods such as pomegranates, raspberries, blueberries and chestnuts. Uro B has recently garnered considerable attention owing to its wide range of nutraceutical effects and relatively high potency. According to several studies, Uro B prevents the development of hyperlipidemia, cardiovascular disease (CVD) and tumors due to its strong antioxidant and anti-inflammatory properties. Many reviews have systematically summarized the health benefits and pharmacological activities of ETs, EA and urolithins (especially Uro A) while available reviews or detailed summaries on the positive impact of Uro B are rarer. Here, we sought to review the pharmacological activity, mechanism of action, regulation of immune function and its associated diseases and preventive potential of Uro B to elucidate its function as a nutritional agent in humans.
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Affiliation(s)
- Peng Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhiei Guo
- Department of Pharmacy, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fuchao Chen
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China
| | - Yue Wu
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Benhong Zhou
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Benhong Zhou,
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11
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Bouyahya A, Omari NE, EL Hachlafi N, Jemly ME, Hakkour M, Balahbib A, El Menyiy N, Bakrim S, Naceiri Mrabti H, Khouchlaa A, Mahomoodally MF, Catauro M, Montesano D, Zengin G. Chemical Compounds of Berry-Derived Polyphenols and Their Effects on Gut Microbiota, Inflammation, and Cancer. Molecules 2022; 27:3286. [PMID: 35630763 PMCID: PMC9146061 DOI: 10.3390/molecules27103286] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/27/2022] [Accepted: 05/08/2022] [Indexed: 12/15/2022] Open
Abstract
Berry-derived polyphenols are bioactive compounds synthesized and secreted by several berry fruits. These polyphenols feature a diversity of chemical compounds, including phenolic acids and flavonoids. Here, we report the beneficial health effects of berry-derived polyphenols and their therapeutical application on gut-microbiota-related diseases, including inflammation and cancer. Pharmacokinetic investigations have confirmed the absorption, availability, and metabolism of berry-derived polyphenols. In vitro and in vivo tests, as well as clinical trials, showed that berry-derived polyphenols can positively modulate the gut microbiota, inhibiting inflammation and cancer development. Indeed, these compounds inhibit the growth of pathogenic bacteria and also promote beneficial bacteria. Moreover, berry-derived polyphenols exhibit therapeutic effects against different gut-microbiota-related disorders such as inflammation, cancer, and metabolic disorders. Moreover, these polyphenols can manage the inflammation via various mechanisms, in particular the inhibition of the transcriptional factor Nf-κB. Berry-derived polyphenols have also shown remarkable effects on different types of cancer, including colorectal, breast, esophageal, and prostate cancer. Moreover, certain metabolic disorders such as diabetes and atherosclerosis were also managed by berry-derived polyphenols through different mechanisms. These data showed that polyphenols from berries are a promising source of bioactive compounds capable of modulating the intestinal microbiota, and therefore managing cancer and associated metabolic diseases. However, further investigations should be carried out to determine the mechanisms of action of berry-derived polyphenol bioactive compounds to validate their safety and examinate their clinical uses.
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Affiliation(s)
- Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
| | - Nasreddine El Omari
- Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10100, Morocco;
| | - Naoufal EL Hachlafi
- Microbial Biotechnology and Bioactive Molecules Laboratory, Sciences and Technologies Faculty, Sidi Mohmed Ben Abdellah University, Imouzzer Road Fez, Fez 30003, Morocco;
| | - Meryem El Jemly
- Faculty of Pharmacy, University Mohammed VI for Health Science, Casablanca 82403, Morocco;
| | - Maryam Hakkour
- Laboratory of Biodiversity, Ecology, and Genome, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco; (M.H.); (A.B.)
| | - Abdelaali Balahbib
- Laboratory of Biodiversity, Ecology, and Genome, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco; (M.H.); (A.B.)
| | - Naoual El Menyiy
- Laboratory of Pharmacology, National Agency of Medicinal and Aromatic Plants, Taounate 34025, Morocco;
| | - Saad Bakrim
- Molecular Engineering, Valorization and Environment Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, Agadir 80000, Morocco;
| | - Hanae Naceiri Mrabti
- Laboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat 10000, Morocco;
| | - Aya Khouchlaa
- Laboratory of Biochemistry, National Agency of Medicinal and Aromatic Plants, Taounate 34025, Morocco;
| | - Mohamad Fawzi Mahomoodally
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Reduit 80837, Mauritius;
| | - Michelina Catauro
- Department of Engineering, University of Campania “Luigi Vanvitelli”, Via Roma 29, 81031 Aversa, Italy
| | - Domenico Montesano
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy;
| | - Gokhan Zengin
- Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, 42130 Konya, Turkey
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12
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Kamal N, Ilowefah MA, Hilles AR, Anua NA, Awin T, Alshwyeh HA, Aldosary SK, Jambocus NGS, Alosaimi AA, Rahman A, Mahmood S, Mediani A. Genesis and Mechanism of Some Cancer Types and an Overview on the Role of Diet and Nutrition in Cancer Prevention. Molecules 2022; 27:1794. [PMID: 35335158 PMCID: PMC8955916 DOI: 10.3390/molecules27061794] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 02/28/2022] [Accepted: 03/07/2022] [Indexed: 02/01/2023] Open
Abstract
Cancer is a major disease with a high mortality rate worldwide. In many countries, cancer is considered to be the second most common cause of death after cardiovascular disease. The clinical management of cancer continues to be a challenge as conventional treatments, such as chemotherapy and radiation therapy, have limitations due to their toxicity profiles. Unhealthy lifestyle and poor dietary habits are the key risk factors for cancer; having a healthy diet and lifestyle may minimize the risk. Epidemiological studies have shown that a high fruit and vegetable intake in our regular diet can effectively reduce the risk of developing certain types of cancers due to the high contents of antioxidants and phytochemicals. In vitro and in vivo studies have shown that phytochemicals exert significant anticancer effects due to their free radical scavenging capacity potential. There has been extensive research on the protective effects of phytochemicals in different types of cancers. This review attempts to give an overview of the etiology of different types of cancers and assesses the role of phytonutrients in the prevention of cancers, which makes the present review distinct from the others available.
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Affiliation(s)
- Nurkhalida Kamal
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia; (N.K.); (N.A.A.)
| | - Muna Abdulsalam Ilowefah
- Department of Food Technology, Faculty of Engineering and Technology, Sabha University, Sabha 00218, Libya;
| | - Ayah Rebhi Hilles
- Institute for Halal Research and Training (INHART), International Islamic University Malaysia, Kuala Lumpur 53100, Malaysia;
| | - Nurul Adlina Anua
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia; (N.K.); (N.A.A.)
| | - Tahani Awin
- Department of Chemistry, Faculty of Science, University of Benghazi, Qar Yunis, Benghazi 5341, Libya;
| | - Hussah Abdullah Alshwyeh
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (H.A.A.); (S.K.A.); (A.A.A.)
- Basic & Applied Scientific Research Centre, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Sahar Khamees Aldosary
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (H.A.A.); (S.K.A.); (A.A.A.)
| | - Najla Gooda Sahib Jambocus
- Ministry of Education, Tertiary Education, Science and Technology, MITD House, Phoenix 73544, Mauritius;
| | - Areej A. Alosaimi
- Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia; (H.A.A.); (S.K.A.); (A.A.A.)
| | - Azizur Rahman
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia;
| | - Syed Mahmood
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Ahmed Mediani
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia; (N.K.); (N.A.A.)
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Teslić N, Santos F, Oliveira F, Stupar A, Pojić M, Mandić A, Pavlić B, Kljakić AC, Duarte ARC, Paiva A, Mišan A. Simultaneous Hydrolysis of Ellagitannins and Extraction of Ellagic Acid from Defatted Raspberry Seeds Using Natural Deep Eutectic Solvents (NADES). Antioxidants (Basel) 2022; 11:254. [PMID: 35204137 PMCID: PMC8868079 DOI: 10.3390/antiox11020254] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/14/2022] [Accepted: 01/18/2022] [Indexed: 11/16/2022] Open
Abstract
Defatted raspberry seeds were used as an alternative source of antioxidants and ellagic acid (EA) extracted using Natural deep eutectic solvents (NADES). In the preliminary study, the best NADES combination (citric acid-betaine) and the most influential variables (temperature, time, and NADES/plant ratio) were selected for the further optimization process. All samples were analyzed in terms of total polyphenol, EA content, and antioxidant activity. Two sets of optimal conditions were generated by response surface methodology. The first set (Opt1) was designed for higher conversion of ellagitannins to EA while the latter set (Opt2) for higher EA content/100 g extract. Opt1 and Opt2 had higher values for all investigated responses compared to 80% ethanolic extract but had a lower conversion rate of ellagitannins to EA compared to acidified methanol extract. The third set of parameters (Opt3) selected beyond the initial experimental domain was used to obtain a sample with the highest EA content/100 g extract. Due to their nature, NADES extracts are ready to use and could have various technological roles in products since they are antioxidants, acidifiers, and colorants. NADES raspberry extracts exhibited higher anti-proliferative activity compared to ethanolic extracts in terms of EC50 values. However, the main contributor of anti-cancer activity in NADES raspberry extracts were individual NADES compounds and/or their newly formed NADES structure.
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Affiliation(s)
- Nemanja Teslić
- Institute of Food Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia; (A.S.); (M.P.); (A.M.); (A.M.)
| | - Filipa Santos
- LAQV, REQUIMTE, Departamento de Química, Nova School of Science and Technology, 2829-516 Caparica, Portugal; (F.S.); (F.O.); (A.R.C.D.); (A.P.)
| | - Filipe Oliveira
- LAQV, REQUIMTE, Departamento de Química, Nova School of Science and Technology, 2829-516 Caparica, Portugal; (F.S.); (F.O.); (A.R.C.D.); (A.P.)
| | - Alena Stupar
- Institute of Food Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia; (A.S.); (M.P.); (A.M.); (A.M.)
| | - Milica Pojić
- Institute of Food Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia; (A.S.); (M.P.); (A.M.); (A.M.)
| | - Anamarija Mandić
- Institute of Food Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia; (A.S.); (M.P.); (A.M.); (A.M.)
| | - Branimir Pavlić
- Faculty of Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia; (B.P.); (A.C.K.)
| | | | - Ana Rita C. Duarte
- LAQV, REQUIMTE, Departamento de Química, Nova School of Science and Technology, 2829-516 Caparica, Portugal; (F.S.); (F.O.); (A.R.C.D.); (A.P.)
| | - Alexandre Paiva
- LAQV, REQUIMTE, Departamento de Química, Nova School of Science and Technology, 2829-516 Caparica, Portugal; (F.S.); (F.O.); (A.R.C.D.); (A.P.)
| | - Aleksandra Mišan
- Institute of Food Technology, University of Novi Sad, Blvd. cara Lazara 1, 21000 Novi Sad, Serbia; (A.S.); (M.P.); (A.M.); (A.M.)
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14
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Al-Harbi SA, Abdulrahman AO, Zamzami MA, Khan MI. Urolithins: The Gut Based Polyphenol Metabolites of Ellagitannins in Cancer Prevention, a Review. Front Nutr 2021; 8:647582. [PMID: 34164422 PMCID: PMC8215145 DOI: 10.3389/fnut.2021.647582] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 04/28/2021] [Indexed: 12/17/2022] Open
Abstract
Cancer as a disease continues to ravage the world population without regard to sex, age, and race. Due to the growing number of cases worldwide, cancer exerts a significant negative impact on global health and the economy. Interestingly, chemotherapy has been used over the years as a therapeutic intervention against cancer. However, high cost, resistance, and toxic by-effects to treatment have overshadowed some of its benefits. In recent times, efforts have been ongoing in searching for anticancer therapeutics of plant origin, focusing on polyphenols. Urolithins are secondary polyphenol metabolites derived from the gut microbial action on ellagitannins and ellagic acid-rich foods such as pomegranate, berries, and nuts. Urolithins are emerging as a new class of anticancer compounds that can mediate their cancer-preventive activities through cell cycle arrest, aromatase inhibition, induction of apoptosis, tumor suppression, promotion of autophagy, and senescence, transcriptional regulation of oncogenes, and growth factor receptors. In this review, we discussed the growing shreds of evidence supporting these secondary phenolic metabolites' anticancer properties. Furthermore, we have pointed out some of the future directions needed to establish urolithins as anticancer agents.
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Affiliation(s)
- Sami A Al-Harbi
- Department of Chemistry, University College in Al-Jamoum, Umm Al-Qura University, Makkah, Saudi Arabia
| | | | - Mazin A Zamzami
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammad Imran Khan
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
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15
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Lee S, Choi H, Park Y, Jung HJ, Ullah S, Choi I, Kang D, Park C, Ryu IY, Jeong Y, Hwang Y, Hong S, Chun P, Moon HR. Urolithin and Reduced Urolithin Derivatives as Potent Inhibitors of Tyrosinase and Melanogenesis: Importance of the 4-Substituted Resorcinol Moiety. Int J Mol Sci 2021; 22:ijms22115616. [PMID: 34070680 PMCID: PMC8199067 DOI: 10.3390/ijms22115616] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/17/2021] [Accepted: 05/22/2021] [Indexed: 12/17/2022] Open
Abstract
We previously reported (E)-β-phenyl-α,β-unsaturated carbonyl scaffold ((E)-PUSC) played an important role in showing high tyrosinase inhibitory activity and that derivatives with a 4-substituted resorcinol moiety as the β-phenyl group of the scaffold resulted in the greatest tyrosinase inhibitory activity. To examine whether the 4-substituted resorcinol moiety could impart tyrosinase inhibitory activity in the absence of the α,β-unsaturated carbonyl moiety of the (E)-PUSC scaffold, 10 urolithin derivatives were synthesized. To obtain more candidate samples, the lactone ring in synthesized urolithins was reduced to produce nine reduced urolithins. Compounds 1c (IC50 = 18.09 ± 0.25 μM), 1h (IC50 = 4.14 ± 0.10 μM), and 2a (IC50 = 15.69 ± 0.40 μM) had greater mushroom tyrosinase-inhibitory activities than kojic acid (KA) (IC50 = 48.62 ± 3.38 μM). The SAR results suggest that the 4-substituted resorcinol motif makes an important contribution to tyrosinase inhibition. To investigate whether these compounds bind to human tyrosinase, a human tyrosinase homology model was developed. Docking simulations with mushroom and human tyrosinases showed that 1c, 1h, and 2a bind to the active site of both tyrosinases with higher binding affinities than KA. Pharmacophore analyses showed that two hydroxyl groups of the 4-substituted resorcinol entity act as hydrogen bond donors in both mushroom and human tyrosinases. Kinetic analyses indicated that these compounds were all competitive inhibitors. Compound 2a inhibited cellular tyrosinase activity and melanogenesis in α-MSH plus IBMX-stimulated B16F10 melanoma cells more strongly than KA. These results suggest that 2a is a promising candidate for the treatment of skin pigment disorders, and show the 4-substituted resorcinol entity importantly contributes to tyrosinase inhibition.
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Affiliation(s)
- Sanggwon Lee
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Heejeong Choi
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Yujin Park
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Hee Jin Jung
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Sultan Ullah
- Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA;
| | - Inkyu Choi
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Dongwan Kang
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Chaeun Park
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Il Young Ryu
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Yeongmu Jeong
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - YeJi Hwang
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Sojeong Hong
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
| | - Pusoon Chun
- College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Korea;
| | - Hyung Ryong Moon
- College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (H.C.); (Y.P.); (H.J.J.); (I.C.); (D.K.); (C.P.); (I.Y.R.); (Y.J.); (Y.H.); (S.H.)
- Correspondence: ; Tel.: +82-51-510-2815; Fax: +82-51-513-6754
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16
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El-Wetidy MS, Ahmad R, Rady I, Helal H, Rady MI, Vaali-Mohammed MA, Al-Khayal K, Traiki TB, Abdulla MH. Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells. Cell Stress Chaperones 2021; 26:473-493. [PMID: 33666815 PMCID: PMC8065090 DOI: 10.1007/s12192-020-01189-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 12/15/2020] [Accepted: 12/21/2020] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common gastrointestinal cancer globally. Prevention of tumor cell proliferation and metastasis is vital for prolonging patient survival. Polyphenols provide a wide range of health benefits and prevention from cancer. In the gut, urolithins are the major metabolites of polyphenols. The objective of our study was to elucidate the molecular mechanism of the anticancer effect of urolithin A (UA) on colorectal cancer cells. UA was found to inhibit the cell proliferation of CRC cell lines in a dose-dependent and time-dependent manner in HT29, SW480, and SW620 cells. Exposure to UA resulted in cell cycle arrest in a dose-dependent manner along with alteration in the expression of cell cycle-related protein. Treatment of CRC cell lines with UA resulted in the induction of apoptosis. Treatment of HT29, SW480, and SW620 with UA resulted in increased expression of the pro-apoptotic proteins, p53 and p21. Similarly, UA treatment inhibited the anti-apoptotic protein expression of Bcl-2. Moreover, exposure of UA induced cytochrome c release and caspase activation. Furthermore, UA was found to generate reactive oxygen species (ROS) production in CRC cells. These findings indicate that UA possesses anticancer potential and may be used therapeutically for the treatment of CRC.
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Affiliation(s)
- Mohammad S El-Wetidy
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt
- College of Medicine Research Center, King Saud University, Riyadh, 11461, Kingdom of Saudi Arabia
| | - Rehan Ahmad
- Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia.
| | - Islam Rady
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt
- Department of Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Hamed Helal
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt
| | - Mohamad I Rady
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt
| | - Mansoor-Ali Vaali-Mohammed
- Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia
| | - Khayal Al-Khayal
- Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia
| | - Thamer Bin Traiki
- Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia
| | - Maha-Hamadien Abdulla
- Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia.
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17
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Madrigal‐Gamboa V, Jiménez‐Arias J, Hidalgo O, Quesada S, Pérez AM, Azofeifa G. Membrane processing effect of blackberry (
Rubus adenotrichos
) on cytotoxic and pro‐apoptotic activities against cancer cell lines. J FOOD PROCESS PRES 2021. [DOI: 10.1111/jfpp.15575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
| | - Johan Jiménez‐Arias
- Centro Nacional de Ciencia y Tecnología de Alimentos (CITA) Universidad de Costa Rica San José Costa Rica
| | - Olman Hidalgo
- Instituto de Investigaciones Farmacéuticas Universidad de Costa Rica San José Costa Rica
| | - Silvia Quesada
- Departamento de Bioquímica Escuela de Medicina Universidad de Costa Rica San José Costa Rica
| | - Ana M. Pérez
- Centro Nacional de Ciencia y Tecnología de Alimentos (CITA) Universidad de Costa Rica San José Costa Rica
| | - Gabriela Azofeifa
- Departamento de Bioquímica Escuela de Medicina Universidad de Costa Rica San José Costa Rica
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18
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Sharma M, Usmani Z, Gupta VK, Bhat R. Valorization of fruits and vegetable wastes and by-products to produce natural pigments. Crit Rev Biotechnol 2021; 41:535-563. [PMID: 33634717 DOI: 10.1080/07388551.2021.1873240] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Synthetic pigments from petrochemicals have been extensively used in a wide range of food products. However, these pigments have adverse effects on human health that has rendered it obligatory to the scientific community in order to explore for much safer, natural, and eco-friendly pigments. In this regard, exploiting the potential of agri-food wastes presumes importance, extracted mainly by employing green processing and extraction technologies. Of late, pigments market size is growing rapidly owing to their extensive uses. Hence, there is a need for sustainable production of pigments from renewable bioresources. Valorization of vegetal wastes (fruits and vegetables) and their by-products (e.g. peels, seeds or pomace) can meet the demands of natural pigment production at the industrial levels for potential food, pharmaceuticals, and cosmeceuticals applications. These wastes/by-products are a rich source of natural pigments such as: anthocyanins, betalains, carotenoids, and chlorophylls. It is envisaged that these natural pigments can contribute significantly to the development of functional foods as well as impart rich biotherapeutic potential. With a sustainability approach, we have critically reviewed vital research information and developments made on natural pigments from vegetal wastes, greener extraction and processing technologies, encapsulation techniques and potential bioactivities. Designed with an eco-friendly approach, it is expected that this review will benefit not only the concerned industries but also be of use to health-conscious consumers.
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Affiliation(s)
- Minaxi Sharma
- ERA-Chair for Food (By-) Products Valorisation Technologies (VALORTECH), Estonian University of Life Sciences, Tartu, Estonia
| | - Zeba Usmani
- Department of Chemistry and Biotechnology, Tallinn University of Technology (TalTech), Tallinn, Estonia
| | - Vijai Kumar Gupta
- Center for Safe and Improved Food, Scotland's Rural College (SRUC), Kings Buildings, Edinburgh, UK.,Biorefining and Advanced Materials Research Center, Scotland's Rural College (SRUC), Kings Buildings, Edinburgh, UK
| | - Rajeev Bhat
- ERA-Chair for Food (By-) Products Valorisation Technologies (VALORTECH), Estonian University of Life Sciences, Tartu, Estonia
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19
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Kim JH, Kim YS, Kim TI, Li W, Mun JG, Jeon HD, Kee JY, Choi JG, Chung HS. Unripe Black Raspberry ( Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction. Foods 2020; 9:foods9111590. [PMID: 33147777 PMCID: PMC7693366 DOI: 10.3390/foods9111590] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022] Open
Abstract
Rubus coreanus Miquel (R. coreanus) is a unripen fruit of black raspberry native to eastern Asia. It is used as traditional oriental medicine and supplementary foods for centuries. Previous studies have shown that the R. coreanus extract (RCE) and its main constitute ellagic acid possess diverse biological activities. However, the effects of RCE on antitumor immunity and T cell function were not fully understood. The present study describes the anti-tumor effect of RCE in humanized PD-1 mice by blocking PD-1/PD-L1 interaction. Competitive enzyme-linked immunosorbent assay (ELISA) and pull down assay were performed to elucidate the binding properties of RCE in vitro. Cellular PD-1/PD-L1 blockade activities were measured by T cell receptor (TCR)-induced nuclear factor of activated T cells-luciferase activity in co-cultured cell models with PD-1/NFAT Jurkat and PD-L1/aAPC CHO-K1 cells. The in vivo efficacy of RCE was confirmed in humanized PD-1 mice bearing MC38 colorectal tumor. RCE and ellagic acid dose-dependently block the binding of PD-1 to PD-L1. Moreover, oral administration of RCE showed the potent anti-tumor activity similar to anti-PD-1 antibody. The present study suggests that RCE possesses potent anti-tumor effect via PD-1/PD-L1 blockade, and ellagic acid is the main compound in RCE. Thus, we provide new aspects of RCE as an immunotherapeutic agent.
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Affiliation(s)
- Ji Hye Kim
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea; (J.H.K.); (Y.S.K.); (T.I.K.); (W.L.)
| | - Young Soo Kim
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea; (J.H.K.); (Y.S.K.); (T.I.K.); (W.L.)
| | - Tae In Kim
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea; (J.H.K.); (Y.S.K.); (T.I.K.); (W.L.)
| | - Wei Li
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea; (J.H.K.); (Y.S.K.); (T.I.K.); (W.L.)
| | - Jeong-Geon Mun
- Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea; (J.-G.M.); (H.D.J.); (J.-Y.K.)
| | - Hee Dong Jeon
- Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea; (J.-G.M.); (H.D.J.); (J.-Y.K.)
| | - Ji-Ye Kee
- Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea; (J.-G.M.); (H.D.J.); (J.-Y.K.)
| | - Jang-Gi Choi
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea; (J.H.K.); (Y.S.K.); (T.I.K.); (W.L.)
- Correspondence: (J.-G.C.); (H.-S.C.); Tel.: +82-53-940-3865 (J.-G.C.); +82-53-940-3875 (H.-S.C.)
| | - Hwan-Suck Chung
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea; (J.H.K.); (Y.S.K.); (T.I.K.); (W.L.)
- Correspondence: (J.-G.C.); (H.-S.C.); Tel.: +82-53-940-3865 (J.-G.C.); +82-53-940-3875 (H.-S.C.)
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20
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Peiffer DS. Modulation of the host microbiome by black raspberries or their components and the therapeutic implications in cancer. FOOD FRONTIERS 2020. [DOI: 10.1002/fft2.40] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Daniel S Peiffer
- Health Sciences Division Loyola University Chicago Maywood Illinois
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21
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Lizardo RCM, Cho H, Lee J, Won Y, Seo K. Extracts of
Elaeagnus multiflora
Thunb. fruit fermented by lactic acid bacteria inhibit SW480 human colon adenocarcinoma via induction of cell cycle arrest and suppression of metastatic potential. J Food Sci 2020. [DOI: 10.1111/1750-3841.15300] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Rona Camille M. Lizardo
- Institute of Food Science and Technology University of the Philippines Los Baños Laguna 4031 Philippines
- Department of Biotechnology Dong‐A University Busan 49315 Republic of Korea
| | - Hyun‐Dong Cho
- Division of Agriculture, Department of Food Science University of Arkansas Fayetteville AR 72704 U.S.A
| | - Jin‐Hwan Lee
- Department of Life Resources Industry Dong‐A University Busan 49315 Republic of Korea
| | - Yeong‐Seon Won
- Department of Biotechnology Dong‐A University Busan 49315 Republic of Korea
| | - Kwon‐Il Seo
- Department of Biotechnology Dong‐A University Busan 49315 Republic of Korea
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22
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Kujawska M, Jodynis-Liebert J. Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection. World J Gastroenterol 2020; 26:3170-3181. [PMID: 32684733 PMCID: PMC7336321 DOI: 10.3748/wjg.v26.i23.3170] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/19/2020] [Accepted: 05/23/2020] [Indexed: 02/06/2023] Open
Abstract
Urolithin A (UA) is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria. The physiologically relevant micromolar concentrations of UA, achieved in the plasma and gastrointestinal tract (GI) after consumption of its dietary precursors, have been revealed to offer GI protection. The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects. UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity, including those involved in carcinogen biotransformation and antioxidant defense. The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract. The data presented herein, covering both studies on the pure compound and in vivo generated UA form its natural precursor, support the potential of this metabolite in treatment interventions against GI ailments.
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Affiliation(s)
- Małgorzata Kujawska
- Department of Toxicology, Poznan University of Medical Sciences, Poznan 60631, Poland
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23
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Majewski M, Kucharczyk E, Kaliszan R, Markuszewski M, Fotschki B, Juśkiewicz J, Borkowska-Sztachańska M, Ognik K. The Characterization of Ground Raspberry Seeds and the Physiological Response to Supplementation in Hypertensive and Normotensive Rats. Nutrients 2020; 12:E1630. [PMID: 32492905 PMCID: PMC7352221 DOI: 10.3390/nu12061630] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 05/25/2020] [Accepted: 05/27/2020] [Indexed: 12/12/2022] Open
Abstract
This study aimed to evaluate the protective role of ground raspberry seeds (RBS) as a source of polyphenols and essential fatty acids on blood plasma enzymatic antioxidant status, lipid profile, and endothelium-intact vasodilation during physiological and pathological conditions. Young normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) at ten weeks of age were fed with either a control diet or were supplemented with added 7% RBS for six weeks (n = 6). The main component of RBS was dietary fiber (64%) and the main polyphenols were ellagitannins (1.2%) and flavan-3-ols (0.45%). Irrespective of the rat model, ground RBS decreased liver enzyme aspartate aminotransferase (0.9-fold) and hydrogen peroxide scavenging capacity (Catalase, 0.9-fold). In supplemented SHRs, preincubation with inducible nitric oxide synthase (iNOS) inhibitor 1400W, nonselective cyclooxygenase (COX) inhibitor indomethacin, selective COX-2 inhibitor NS-398, prostacyclin (PGI2) synthesis inhibitor tranylcypromine (TCP), thromboxane receptor (TP) antagonist SQ-29548, thromboxane synthesis inhibitor furegrelate, and 20-HETE synthesis inhibitor HET0016 induced the same relaxant response to acetylcholine as in the nonsupplemented control group. In supplemented WKYs, atherogenic index was decreased (0.8-fold), while iNOS and COX-2-derived PGI2 increased acetylcholine-induced vasodilation. These effects of ground RBS may constitute a potential mechanism for preventing cardiovascular diseases.
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Affiliation(s)
- Michał Majewski
- Department of Pharmacology and Toxicology, Faculty of Medicine, UWM, 10-082 Olsztyn, Poland;
| | - Ewa Kucharczyk
- Department of Pharmacology and Toxicology, Faculty of Medicine, UWM, 10-082 Olsztyn, Poland;
| | - Roman Kaliszan
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Hallera 107, 80-416 Gdansk, Poland; (R.K.); (M.M.)
| | - Michał Markuszewski
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Hallera 107, 80-416 Gdansk, Poland; (R.K.); (M.M.)
| | - Bartosz Fotschki
- Division of Food Science, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10-748 Olsztyn, Poland; (B.F.); (J.J.)
| | - Jerzy Juśkiewicz
- Division of Food Science, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10-748 Olsztyn, Poland; (B.F.); (J.J.)
| | | | - Katarzyna Ognik
- Department of Biochemistry and Toxicology, Faculty of Biology, Animal Sciences and Bioeconomy, University of Life Sciences, 20-950 Lublin, Poland;
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24
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Cheshomi H, Bahrami AR, Matin MM. Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action. Mol Divers 2020; 25:333-349. [PMID: 32410114 DOI: 10.1007/s11030-020-10101-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 04/28/2020] [Indexed: 12/27/2022]
Abstract
Research on anticancer properties of natural compounds, as effective materials that are available while causing minimal side effects, is growing. Ellagic acid (EA) is a well-known polyphenolic compound, which has been found in both free and complex modes in several medicinal plants such as pomegranate, walnut, and berries. Although many articles have reported anticancer properties for this compound, its mechanism of action has not been fully elucidated. In this study, we used several online and offline bioinformatics tools and databases to identify the mechanism of action of EA on various types of human malignancies including bladder, blood, breast, cervical, colorectal, liver, pancreas, and prostate cancers. In this context, after identifying and extracting EA-affected human genes/proteins that have been reported in various references, we built the related gene networks and determined functional hub genes. In addition, docking was performed to recognize target proteins that react directly with EA and are in fact most affected by this compound. Our findings revealed that EA exerts its anticancer effects by influencing specific hub genes in various types of cancers. Moreover, different cellular signaling pathways are affected by this natural compound. Generally, it turned out that EA probably exerts most of its anticancer activities, through induction of apoptosis, as well as P53 and WNT signaling pathways, and also by affecting the expression of several hub genes such as CDKN1A, CDK4, CDK2, CDK6, TP53, JUN, CCNA2, MAPK14, CDK1, and CCNB1 and especially interactions with some related proteins including P53, CDK6, and MAPK14.
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Affiliation(s)
- Hamid Cheshomi
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Ahmad Reza Bahrami
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
- Stem Cell and Regenerative Medicine Research Group, Iranian Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, Mashhad, Iran
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
- Stem Cell and Regenerative Medicine Research Group, Iranian Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, Mashhad, Iran.
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25
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Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:1675957. [PMID: 32377290 PMCID: PMC7196981 DOI: 10.1155/2020/1675957] [Citation(s) in RCA: 132] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 03/14/2020] [Accepted: 04/06/2020] [Indexed: 12/30/2022]
Abstract
The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.
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26
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Fierascu RC, Sieniawska E, Ortan A, Fierascu I, Xiao J. Fruits By-Products - A Source of Valuable Active Principles. A Short Review. Front Bioeng Biotechnol 2020; 8:319. [PMID: 32351951 PMCID: PMC7174504 DOI: 10.3389/fbioe.2020.00319] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 03/24/2020] [Indexed: 02/05/2023] Open
Abstract
The growing demand for more sustainable, alternative processes leading to production of plant-derived preparations imposes the use of plants waste generated mainly by agri-food and pharmaceutical industries. These mostly unexploited but large quantities of plants waste also increase the interest in developing alternative approaches for sustainable production of therapeutic molecules. In order to reduce the amount of plant waste by further processing, different novel extraction techniques can be applied. Fruits and their industrial by-products are rich sources of different classes of compounds with therapeutic properties. The processed fruits waste can be reused and lead to novel pharmaceuticals, food supplements or functional foods. This review intends to briefly summarize recent aspects regarding the production of different active compounds from fruit by-products, and their therapeutic properties. The potential use of fruits by-products in different industries will be also discussed.
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Affiliation(s)
- Radu C. Fierascu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Bucharest, Romania
- The National Institute for Research & Development in Chemistry and Petrochemistry-ICECHIM, Emerging Nanotechnologies Group, Bucharest, Romania
| | - Elwira Sieniawska
- Department of Pharmacognosy, Medical University of Lublin, Lublin, Poland
| | - Alina Ortan
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Bucharest, Romania
| | - Irina Fierascu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Bucharest, Romania
- The National Institute for Research & Development in Chemistry and Petrochemistry-ICECHIM, Emerging Nanotechnologies Group, Bucharest, Romania
| | - Jianbo Xiao
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
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27
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Liberal J, Costa G, Carmo A, Vitorino R, Marques C, Domingues MR, Domingues P, Gonçalves AC, Alves R, Sarmento-Ribeiro AB, Girão H, Cruz MT, Batista MT. Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves. ARAB J CHEM 2019. [DOI: 10.1016/j.arabjc.2015.11.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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28
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Chen T, Shi N, Afzali A. Chemopreventive Effects of Strawberry and Black Raspberry on Colorectal Cancer in Inflammatory Bowel Disease. Nutrients 2019; 11:E1261. [PMID: 31163684 PMCID: PMC6627270 DOI: 10.3390/nu11061261] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 05/24/2019] [Accepted: 05/27/2019] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer (CRC) remains the third most common cause of cancer-related death in the United States and the fourth globally with a rising incidence. Inflammatory bowel disease (IBD) is a chronic immunologically mediated disease that imposes a significant associated health burden, including the increased risk for colonic dysplasia and CRC. Carcinogenesis has been attributed to chronic inflammation and associated with oxidative stress, genomic instability, and immune effectors as well as the cytokine dysregulation and activation of the nuclear factor kappa B (NFκB) signaling pathway. Current anti-inflammation therapies used for IBD treatment have shown limited effects on CRC chemoprevention, and their long-term toxicity has limited their clinical application. However, natural food-based prevention approaches may offer significant cancer prevention effects with very low toxicity profiles. In particular, in preclinical and clinical pilot studies, strawberry and black raspberry have been widely selected as food-based interventions because of their potent preventive activities. In this review, we summarize the roles of strawberry, black raspberry, and their polyphenol components on CRC chemoprevention in IBD.
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Affiliation(s)
- Tong Chen
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
| | - Ni Shi
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
| | - Anita Afzali
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Columbus, OH 43210, USA.
- Inflammatory Bowel Disease Center, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
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29
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Zheng J, Heber D, Wang M, Gao C, Heymsfield SB, Martin RJ, Greenway FL, Finley JW, Burton JH, Johnson WD, Enright FM, Keenan MJ, Li Z. Pomegranate juice and extract extended lifespan and reduced intestinal fat deposition in Caenorhabditis elegans. INT J VITAM NUTR RES 2019; 87:149-158. [PMID: 31084484 DOI: 10.1024/0300-9831/a000570] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Pomegranate juice with a high content of polyphenols, pomegranate extract, ellagic acid, and urolithin A, have anti-oxidant and anti-obesity effects in humans. Pomegranate juice extends lifespan of Drosophila melanogaster. Caenorhabditis elegans (C. elegans) (n = 6) compared to the control group in each treatment, lifespan was increased by pomegranate juice in wild type (N2, 56 %, P < 0.001) and daf-16 mutant (daf-16(mgDf50)I) (18 %, P = 0.00012), by pomegranate extract in N2 (28 %, P = 0.00004) and in daf-16(mgDf50)I (10 %, P < 0.05), or by ellagic acid (11 %, P < 0.05). Pomegranate juice reduced intestinal fat deposition (IFD) in C. elegans (n = 10) N2 (-68 %, P = 0.0003) or in the daf-16(mgDf50)I (-33 %, P = 0.0034). The intestinal fat deposition was increased by pomegranate extract in N2 (137 %, P < 0.0138) and in daf-16(mgDf50)I (26 %, P = 0.0225), by ellagic acid in N2 (66 %, P < 0.0001) and in daf-16(mgDf50)I (74 %, P < 0.0001), or by urolithin A in N2 (57 %, P = 0.0039) and in daf-16(mgDf50)I (43 %, P = 0.0001). These effects were partially mediated by the daf-16 pathway. The data may offer insights to human aging and obesity due to homology with C. elegans.
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Affiliation(s)
- Jolene Zheng
- 1 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.,2 School of Nutrition and Food Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - David Heber
- 3 Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Mingming Wang
- 2 School of Nutrition and Food Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - Chenfei Gao
- 2 School of Nutrition and Food Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - Steven B Heymsfield
- 1 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Roy J Martin
- 4 Department of Nutrition, University of California, Davis, CA, USA
| | - Frank L Greenway
- 1 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - John W Finley
- 2 School of Nutrition and Food Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - Jeffrey H Burton
- 1 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - William D Johnson
- 1 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Frederick M Enright
- 5 School of Animal Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - Michael J Keenan
- 1 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.,2 School of Nutrition and Food Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - Zhaoping Li
- 3 Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA
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30
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Lee WL, Yew PN, Lim YY. Tannic acid-rich porcupine bezoars induce apoptosis and cell cycle arrest in human colon cancer cells. Pharmacogn Mag 2019. [DOI: 10.4103/pm.pm_620_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
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31
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Lorenzo JM, Munekata PE, Putnik P, Kovačević DB, Muchenje V, Barba FJ. Sources, Chemistry, and Biological Potential of Ellagitannins and Ellagic Acid Derivatives. STUDIES IN NATURAL PRODUCTS CHEMISTRY 2019. [DOI: 10.1016/b978-0-444-64181-6.00006-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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32
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Afrin S, Giampieri F, Gasparrini M, Forbes-Hernández TY, Cianciosi D, Reboredo-Rodriguez P, Zhang J, Manna PP, Daglia M, Atanasov AG, Battino M. Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved. Biotechnol Adv 2018; 38:107322. [PMID: 30476540 DOI: 10.1016/j.biotechadv.2018.11.011] [Citation(s) in RCA: 104] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 12/11/2022]
Abstract
Worldwide, colorectal cancer (CRC) remains a major cancer type and leading cause of death. Unfortunately, current medical treatments are not sufficient due to lack of effective therapy, adverse side effects, chemoresistance and disease recurrence. In recent decades, epidemiologic observations have highlighted the association between the ingestion of several phytochemical-enriched foods and nutrients and the lower risk of CRC. According to preclinical studies, dietary phytochemicals exert chemopreventive effects on CRC by regulating different markers and signaling pathways; additionally, the gut microbiota plays a role as vital effector in CRC onset and progression, therefore, any dietary alterations in it may affect CRC occurrence. A high number of studies have displayed a key role of growth factors and their signaling pathways in the pathogenesis of CRC. Indeed, the efficiency of dietary phytochemicals to modulate carcinogenic processes through the alteration of different molecular targets, such as Wnt/β-catenin, PI3K/Akt/mTOR, MAPK (p38, JNK and Erk1/2), EGFR/Kras/Braf, TGF-β/Smad2/3, STAT1-STAT3, NF-кB, Nrf2 and cyclin-CDK complexes, has been proven, whereby many of these targets also represent the backbone of modern drug discovery programs. Furthermore, epigenetic analysis showed modified or reversed aberrant epigenetic changes exerted by dietary phytochemicals that led to possible CRC prevention or treatment. Therefore, our aim is to discuss the effects of some common dietary phytochemicals that might be useful in CRC as preventive or therapeutic agents. This review will provide new guidance for research, in order to identify the most studied phytochemicals, their occurrence in foods and to evaluate the therapeutic potential of dietary phytochemicals for the prevention or treatment of CRC by targeting several genes and signaling pathways, as well as epigenetic modifications. In addition, the results obtained by recent investigations aimed at improving the production of these phytochemicals in genetically modified plants have been reported. Overall, clinical data on phytochemicals against CRC are still not sufficient and therefore the preventive impacts of dietary phytochemicals on CRC development deserve further research so as to provide additional insights for human prospective studies.
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Affiliation(s)
- Sadia Afrin
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Francesca Giampieri
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain); Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Massimiliano Gasparrini
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Tamara Y Forbes-Hernández
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain)
| | - Danila Cianciosi
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Patricia Reboredo-Rodriguez
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain)
| | - Jiaojiao Zhang
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Piera Pia Manna
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Pavia 27100, Italy
| | - Atanas Georgiev Atanasov
- Department of Pharmacognosy, University of Vienna, Althanstrasse 14, Vienna 1090, Austria; Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Postępu 36A Street, Jastrzebiec 05-552, Poland.
| | - Maurizio Battino
- Nutrition and Food Science Group, Dept. of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo Campus, Vigo, (Spain); Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
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Battino M, Forbes-Hernández TY, Gasparrini M, Afrin S, Cianciosi D, Zhang J, Manna PP, Reboredo-Rodríguez P, Varela Lopez A, Quiles JL, Mezzetti B, Bompadre S, Xiao J, Giampieri F. Relevance of functional foods in the Mediterranean diet: the role of olive oil, berries and honey in the prevention of cancer and cardiovascular diseases. Crit Rev Food Sci Nutr 2018; 59:893-920. [PMID: 30421983 DOI: 10.1080/10408398.2018.1526165] [Citation(s) in RCA: 98] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 09/13/2018] [Accepted: 09/16/2018] [Indexed: 02/08/2023]
Abstract
The traditional Mediterranean diet (MedDiet) is a well-known dietary pattern associated with longevity and improvement of life quality as it reduces the risk of the most common chronic pathologies, such as cancer and cardiovascular diseases (CVDs), that represent the principal cause of death worldwide. One of the most characteristic foods of MedDiet is olive oil, a very complex matrix, which constitutes the main source of fats and is used in the preparation of foods, both raw as an ingredient in recipes, and in cooking. Similarly, strawberries and raspberries are tasty and powerful foods which are commonly consumed in the Mediterranean area in fresh and processed forms and have attracted the scientific and consumer attention worldwide for their beneficial properties for human health. Besides olive oil and berries, honey has lately been introduced in the MedDiet thanks to its relevant nutritional, phytochemical and antioxidant profile. It is a sweet substance that has recently been classified as a functional food. The aim of this review is to present and discuss the recent evidence, obtained from in vitro, in vivo and epidemiological studies, on the potential roles exerted by these foods in the prevention and progression of different types of cancer and CVDs.
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Affiliation(s)
- Maurizio Battino
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Tamara Y Forbes-Hernández
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Massimiliano Gasparrini
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Sadia Afrin
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Danila Cianciosi
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Jiaojiao Zhang
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Piera P Manna
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
| | - Patricia Reboredo-Rodríguez
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
- b Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Science , University of Vigo, Ourense Campus , Ourense , Spain
| | - Alfonso Varela Lopez
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
- c Department of Physiology , Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada , Granada , Spain
| | - Josè L Quiles
- c Department of Physiology , Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada , Granada , Spain
| | - Bruno Mezzetti
- d Dipartimento di Scienze Agrarie, Alimentari e Ambientali , Università Politecnica delle Marche , Ancona , Italy
| | - Stefano Bompadre
- e Dipartimento di Scienze Biomediche e Sanità Pubblica , Università Politecnica delle Marche , Ancona , Italy
| | - Jianbo Xiao
- f Institute of Chinese Medical Sciences , University of Macau , Taipa , Macau , China
| | - Francesca Giampieri
- a Department of Clinical Sciences, Faculty of Medicine , Università Politecnica delle Marche , Ancona , Ancona , Italy
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Afrin S, Giampieri F, Gasparrini M, Forbes-Hernández TY, Cianciosi D, Reboredo-Rodriguez P, Amici A, Quiles JL, Battino M. The inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cell growth. Part 1: the suppression of cell proliferation, promotion of apoptosis and arrest of the cell cycle. Food Funct 2018; 9:2145-2157. [PMID: 29645049 DOI: 10.1039/c8fo00164b] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid. The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to different concentrations of MH (0-20 mg mL-1 for HCT-116 cells and 0-50 mg mL-1 for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as apoptosis and cell cycle regulatory gene and protein expression. MH exhibited profound inhibitory effects on cellular growth by reducing the proliferation ability, inducing apoptosis and arresting the cell cycle in a dose-dependent manner. Interestingly, MH treatment in non-malignant cells did not exert any significant toxicity at similar concentrations. The apoptosis event was associated with the increasing expression of p53, cleaved-PARP and caspase-3 and with the activation of both intrinsic (caspase-9) and extrinsic (caspase-8) apoptotic pathways. MH induced cell cycle arrest in the S phase in HCT-116 cells, and simultaneously, in LoVo cells, it occurred in the G2/M phase through the modulation of cell cycle regulator genes (cyclin D1, cyclin E, CDK2, CDK4, p21, p27 and Rb). The expression of p-Akt was suppressed while the expression of p-p38MAPK, p-Erk1/2 and endoplasmic stress markers (ATF6 and XBP1) was increased for apoptosis induction. Overall, these findings indicate that MH could be a promising preventive or curative food therapy for colon cancer.
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Affiliation(s)
- Sadia Afrin
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, 60131, Ancona, Italy.
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Zhang H, Liu J, Li G, Wei J, Chen H, Zhang C, Zhao J, Wang Y, Dang S, Li X, Fang X, Liu L, Liu M. Fresh red raspberry phytochemicals suppress the growth of hepatocellular carcinoma cells by PTEN/AKT pathway. Int J Biochem Cell Biol 2018; 104:55-65. [PMID: 30195065 DOI: 10.1016/j.biocel.2018.09.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 08/17/2018] [Accepted: 09/04/2018] [Indexed: 12/24/2022]
Abstract
The red raspberry (Rubus idaeus L.) is a common fruit worldwide and its extract has been found to inhibit the growth of many types of tumors, mainly because it is rich in bioactive phytochemicals. However, the mechanism underlying its anticancer activity in hepatocellular carcinoma (HCC) is not well understood. Herein, the aim of this study was to determine the effects of red raspberry phytochemicals on the proliferation of hepatocellular carcinoma cells and to elucidate its biochemical and molecular targets. CCK8 and colony formation, as well as flow cytometry assays, were employed to determine the effects of red raspberry extract (RRE) on cell proliferation and cell cycle distribution in HCC cells. Our results showed that RRE significantly inhibited cell proliferation and arrested cell cycle progression at the S phase in HCC cells. RRE increased the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) by reducing the methylation status of the PTEN gene promoter and inhibiting DNMT1 expression and regulated AKT signaling pathway. These findings show that red raspberry phytochemicals inhibit the proliferation of HCC cells by regulating PTEN/AKT signaling pathway, providing evidence that RRE may be used as a potential auxiliary therapy for patients with HCC.
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Affiliation(s)
- Haopeng Zhang
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Jiaren Liu
- Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Guodong Li
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Jiufeng Wei
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Hongsheng Chen
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Chunpeng Zhang
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Jinlu Zhao
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Yunfeng Wang
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Shuwei Dang
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Xinglong Li
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Xuan Fang
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Lianxin Liu
- Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University & Key Laboratory of Hepatosplenic Surgery Ministry of Education, Harbin, 150001, China
| | - Ming Liu
- Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
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Zhang X, Sandhu A, Edirisinghe I, Burton-Freeman B. An exploratory study of red raspberry (Rubus idaeus L.) (poly)phenols/metabolites in human biological samples. Food Funct 2018; 9:806-818. [PMID: 29344587 DOI: 10.1039/c7fo00893g] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different forms (parent compounds, degradants or microbial metabolites) are subject to xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate, glucuronide, and sulfate conjugated metabolites. Upon acute exposure, (poly)phenol/metabolite presence in the blood depends mainly on intestinal absorption, enterohepatic circulation, and metabolism by resident microbiota. However, chronic exposure to red raspberry polyphenols may alter metabolite patterns depending on adaptions in the xenobiotic machinery and/or microbiota composition. Understanding the metabolic fate of these compounds and their composition in different biological specimens relative to the exposure time/dose will aid in designing future health benefit studies, including the mechanism of action studies. The present exploratory study applied ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight (QTOF) and triple quadrupole (QQQ) mass spectrometries to characterize red raspberry polyphenols in fruit and then their appearance, including metabolites in human biological samples (plasma, urine and breast milk) after the chronic intake of red raspberries. The results suggested that the most abundant polyphenols in red raspberries included cyanidin 3-O-sophoroside, cyanidin 3-O-glucoside, sanguiin H6 and lambertianin C. Sixty-two (poly)phenolic compounds were tentatively identified in the plasma, urine and breast milk samples after the intake of red raspberries. In general, urine contained the highest content of phenolic metabolites; phase II metabolites, particularly sulfated conjugates, were mainly present in urine and breast milk, and breast milk contained fewer parent anthocyanins compared to urine and plasma.
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Affiliation(s)
- Xuhuiqun Zhang
- Center for Nutrition Research, Institute for Food Safety and Health, Illinois Institute of Technology, IL, USA.
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Banerjee A, Dhar P. Amalgamation of polyphenols and probiotics induce health promotion. Crit Rev Food Sci Nutr 2018; 59:2903-2926. [PMID: 29787290 DOI: 10.1080/10408398.2018.1478795] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The residing microbiome with its vast repertoire of genes provide distinctive properties to the host by which they can degrade and utilise nutrients that otherwise pass the gastro-intestinal tract unchanged. The polyphenols in our diet have selective growth promoting effects which is of utmost importance as the state of good health has been linked to dominance of particular microbial genera. The polyphenols in native form might more skilfully exert anti-oxidative and anti-inflammatory properties but in a living system it is the microbial derivatives of polyphenol that play a key role in determining health outcome. This two way interaction has invoked great interest among researchers who have commenced several clinical surveys and numerous studies in in-vitro, simulated environment and living systems to find out in detail about the biomolecules involved in such interaction along with their subsequent physiological benefits. In this review, we have thoroughly discussed these studies to develop a fair idea on how the amalgamation of probiotics and polyphenol has an immense potential as an adjuvant therapeutic for disease prevention as well as treatment.
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Affiliation(s)
- Arpita Banerjee
- Laboratory of Food Science and Technology, Food and Nutrition Division, University of Calcutta , 20B Judges Court Road, Alipore, Kolkata , West Bengal , India
| | - Pubali Dhar
- Laboratory of Food Science and Technology, Food and Nutrition Division, University of Calcutta , 20B Judges Court Road, Alipore, Kolkata , West Bengal , India
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38
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Zhao W, Shi F, Guo Z, Zhao J, Song X, Yang H. Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells. Mol Carcinog 2017; 57:193-200. [PMID: 28976622 PMCID: PMC5814919 DOI: 10.1002/mc.22746] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 09/20/2017] [Accepted: 09/29/2017] [Indexed: 12/29/2022]
Abstract
Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose‐dependently decreased cell proliferation, delayed cell migration, and decreased matrix metalloproteinas‐9 (MMP‐9) activity. In addition, inhibition of autophagy by Atg5‐siRNA, caspases by Z‐VAD‐FMK suppressed urolithin A‐stimulated cell death and anti‐metastatic effects. Micromolar urolithin A concentrations induced both autophagy and apoptosis. Urolithin A suppressed cell cycle progression and inhibited DNA synthesis. These results suggest that dietary consumption of urolithin A could induce autophagy and inhibit human CRC cell metastasis. Urolithins may thus contribute to CRC treatment and offer an alternative or adjunct chemotherapeutic agent to combat this disease.
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Affiliation(s)
- Wenhua Zhao
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Fengqiang Shi
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Zhikun Guo
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Jiaojie Zhao
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Xueying Song
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
| | - Hua Yang
- School of Pharmaceutical Sciences, Capital Medical University, Beijing, China
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Wu S, Tian L. Diverse Phytochemicals and Bioactivities in the Ancient Fruit and Modern Functional Food Pomegranate (Punica granatum). Molecules 2017; 22:molecules22101606. [PMID: 28946708 PMCID: PMC6151597 DOI: 10.3390/molecules22101606] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 09/21/2017] [Accepted: 09/21/2017] [Indexed: 12/21/2022] Open
Abstract
Having served as a symbolic fruit since ancient times, pomegranate (Punica granatum) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), to the health-promoting activities of pomegranate juice and fruit extracts. However, it remains unclear as to how, and to what extent, the numerous phytochemicals in pomegranate may interact and exert cooperative activities in humans. In this review, we examine the structural and analytical information of the diverse phytochemicals that have been identified in different pomegranate tissues, to establish a knowledge base for characterization of metabolite profiles, discovery of novel phytochemicals, and investigation of phytochemical interactions in pomegranate. We also assess recent findings on the function and molecular mechanism of ATs as well as urolithins, the intestinal microbial derivatives of pomegranate HTs, on human nutrition and health. A better understanding of the structural diversity of pomegranate phytochemicals as well as their bioconversions and bioactivities in humans will facilitate the interrogation of their synergistic/antagonistic interactions and accelerate their applications in dietary-based cancer chemoprevention and treatment in the future.
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Affiliation(s)
- Sheng Wu
- Shanghai Key Laboratory of Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai 201602, China.
- Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai 201602, China.
| | - Li Tian
- Shanghai Key Laboratory of Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai 201602, China.
- Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai 201602, China.
- Department of Plant Sciences, University of California, Davis, CA 95616, USA.
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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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Kamel KM, Khalil IA, Rateb ME, Elgendy H, Elhawary S. Chitosan-Coated Cinnamon/Oregano-Loaded Solid Lipid Nanoparticles to Augment 5-Fluorouracil Cytotoxicity for Colorectal Cancer: Extract Standardization, Nanoparticle Optimization, and Cytotoxicity Evaluation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2017; 65:7966-7981. [PMID: 28813148 DOI: 10.1021/acs.jafc.7b03093] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
This study aimed to coat lipid-based nanocarriers with chitosan to encapsulate nutraceuticals, minimize opsonization, and facilitate passive-targeting. Phase one was concerned with standardization according to the World Health Organization. Qualitative analysis using liquid chromatography-high-resolution mass spectrometry (LC-HRMS/MS) investigated the active constituents, especially reported cytotoxic agents. Cinnamaldehyde and rosmarinic acid were selected to be quantified using high-performance liquid chromatography. Phase two was aimed to encapsulate both extracts in solid lipid nanoparticles (core) and chitosan (shell) to gain the advantages of both materials properties. The developed experimental model suggested an optimum formulation with 2% lipid, 2.3% surfactant, and 0.4% chitosan to achieve a particle size of 254.77 nm, polydispersity index of 0.28, zeta potential of +15.26, and entrapment efficiency percentage of 77.3% and 69.1% for cinnamon and oregano, respectively. Phase three was focused on the evaluation of cytotoxic activity unencapsulated/encapsulated cinnamon and oregano extracts with/without 5-fluorouracil on HCT-116 cells. This study confirmed the success of the suggested combination with 5-fluorouracil for treating human colon carcinoma with a low dose leading to decreasing side effects and allowing uninterrupted therapy.
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Affiliation(s)
| | - Islam A Khalil
- Nanomaterials Lab., Center of Material Science (CMS), Zewail City of Science and Technology , 6th of October, Giza 12588, Egypt
| | - Mostafa E Rateb
- School of Science & Sport, University of the West of Scotland , Paisley PA1 2BE, Scotland U.K
- Pharmacognosy Department, Faculty of Pharmacy, Beni-Suef University , Beni-Suef 62511, Egypt
| | | | - Seham Elhawary
- Pharmacognosy Department, Faculty of Pharmacy, Cairo University , Cairo, Egypt
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Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells. Invest New Drugs 2017. [PMID: 28631098 DOI: 10.1007/s10637-017-0483-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative effects of urolithins A, B and C and ellagic acid on different human tumor cell lines. The evaluation of cell viability and the determination of the half-maximal inhibitory concentrations indicated that the sensitivity to the studied urolithins varied markedly between the different cell lines, with the bladder cancer cells (UMUC3) being the most susceptible. In UMUC3 cells, urolithin A was the most active molecule, promoting cell cycle arrest at the G2/M checkpoint, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signaling. Overall, the present study emphasizes the chemopreventive/chemotherapeutic potential of urolithins, highlighting the stronger effects of urolithin A and its potential to target transitional bladder cancer cells.
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Cui GH, Chen WQ, Shen ZY. Urolithin A shows anti-atherosclerotic activity via activation of class B scavenger receptor and activation of Nef2 signaling pathway. Pharmacol Rep 2017; 70:519-524. [PMID: 29660655 DOI: 10.1016/j.pharep.2017.04.020] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 04/26/2017] [Indexed: 01/20/2023]
Abstract
BACKGROUND This study investigates the therapeutic potential of urothelin A in attenuating atherosclerotic lesion in wistar rat models and explore the role of Scavenger receptor-class B type I (SR-BI) and activation of Nrf-2 singling pathway. METHODS Wistar rats (n=48) were feed with high cholesterol diet supplemented with Vitamin D3 and subjected to balloon injury of the aorta. Three days prior to the aortal injury, rats (n=16) were administered urothelin A (3mg/kg/d; po). Positive control were rats receiving high cholesterol diet and balloon injury of the aorta (n=16). The sham group (n=16) consisted of rats fed on basal diet. After twelve weeks blood was collected from all animals for estimation of lipid and angiotensin II (Ang II) levels along, subsequently all animals were sacrificed and morphologic analysis of the aorta was performed. Expression of SR-BI and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein were evaluated by Western blot. RESULTS After twelve weeks of treatment with urolithin A, there was a significant decrease in the plasma lipid and Ang II levels and improvement of aortic lesion compared with the sham group. There was an increased expression of SR-BI and inhibition of p-ERK1/2 (p<0.05). The expression of SR-BI was inversely correlated with levels of Ang II. CONCLUSION From the results it can be safely concluded that administration of urolithin A attenuates atherosclerosis via upregulation of SR-BI expression and inhibition of p-ERK1/2 levels.
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Affiliation(s)
- Guang-Hao Cui
- Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, China
| | - Wei-Qian Chen
- Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, China
| | - Zhen-Ya Shen
- Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, China.
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Zhao J, Li G, Bo W, Zhou Y, Dang S, Wei J, Li X, Liu M. Multiple effects of ellagic acid on human colorectal carcinoma cells identified by gene expression profile analysis. Int J Oncol 2017; 50:613-621. [PMID: 28101576 DOI: 10.3892/ijo.2017.3843] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 11/25/2016] [Indexed: 11/06/2022] Open
Abstract
Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer in the world. Phytochemicals have become a research hotspot in recent years as cancer prevention and treatment agents due to their low toxicity and limited side-effects. Ellagic acid (EA), a natural phenolic constituent, displays various biological activities, including anticancer effects. However, the detailed anticancer mechanisms of EA remain unclear. In the present study, we found that EA inhibited the growth of HCT-116 colon cancer cells. Moreover, we identified differentially expressed genes (DEGs) by microarray profiling of HCT-116 cells treated with EA. A total of 857 DEGs (363 upregulated and 494 downregulated) were identified with a >1.5-fold change in expression after treatment with EA for 72 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that a large number of cellular functions were modified by EA including proliferation, apoptosis, cell cycle and angiogenesis. Interaction network analysis using DEGs provided details of their interactions and predicted the key target pathways of EA. To verify the result of cDNA microarray, 10 selected DEGs related to proliferation, apoptosis or cell cycle were further confirmed by real-time RT-PCR. Based on microarray data, we identified several crucial functions of EA. These results provide important new data for EA in anti-CRC research.
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Affiliation(s)
- Jinlu Zhao
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Guodong Li
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Wanlan Bo
- Department of Gastroenterology, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Yuhui Zhou
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Shuwei Dang
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Jiufeng Wei
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Xinglong Li
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Ming Liu
- Department of General Surgery, Τhe Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
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Zhang W, Chen JH, Aguilera-Barrantes I, Shiau CW, Sheng X, Wang LS, Stoner GD, Huang YW. Urolithin A suppresses the proliferation of endometrial cancer cells by mediating estrogen receptor-α-dependent gene expression. Mol Nutr Food Res 2016; 60:2387-2395. [PMID: 27342949 DOI: 10.1002/mnfr.201600048] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 06/16/2016] [Accepted: 06/19/2016] [Indexed: 12/14/2022]
Abstract
SCOPE Obese and overweight women are at high risk of developing endometrial cancer; indeed, many of endometrial cancer patients are obese. The increased number and size of adipocytes due to obesity elevate levels of circulating estrogens that stimulate cell proliferation in the endometrium. However, black raspberries are a promising approach to preventing endometrial cancer. METHODS AND RESULTS We examined 17 black raspberry constituents and metabolites (10 μM or 10 μg/mL, 48 h) for their ability to prevent endometrial cancer cells from proliferating. Urolithin A (UA) was most able to suppress proliferation in a time- and dose-dependent manner (p < 0.05). It arrested the G2/M phase of the cell cycle by upregulating cyclin-B1, cyclin-E2, p21, phospho-cdc2, and CDC25B. UA also acted as an estrogen agonist by modulating estrogen receptor-α (ERα) dependent gene expression in ER-positive endometrial cancer cells. UA enhanced the expression of ERβ, PGR, pS2, GREB1 while inhibiting the expression of ERα and GRIP1. Coincubating UA-treated cells with the estrogen antagonist ICI182,780 abolished UA's estrogenic effects. Knocking down ERα suppressed PGR, pS2, and GREB gene expression but increased GRIP1 expression. Thus, UA's actions appear to be mediated through ERα. CONCLUSION This study suggests that UA modulates ERα-dependent gene expression, thereby inhibiting endometrial cancer proliferation.
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Affiliation(s)
- Wei Zhang
- School of Medicine and life Science, University of Jinan-Shandong Academy of Medical Science, Jinan, Shandong, China.,Department of Gynecology Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Jo-Hsin Chen
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Chung-Wai Shiau
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan
| | - Xiugui Sheng
- Department of Gynecology Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Li-Shu Wang
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Gary D Stoner
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Yi-Wen Huang
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA
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Tomás-Barberán FA, González-Sarrías A, García-Villalba R, Núñez-Sánchez MA, Selma MV, García-Conesa MT, Espín JC. Urolithins, the rescue of “old” metabolites to understand a “new” concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res 2016; 61. [DOI: 10.1002/mnfr.201500901] [Citation(s) in RCA: 240] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 04/25/2016] [Accepted: 04/26/2016] [Indexed: 12/14/2022]
Affiliation(s)
| | | | - Rocío García-Villalba
- Research Group on Quality; Safety; and Bioactivity of Plant Foods; CEBAS-CSIC; Murcia Spain
| | - María A. Núñez-Sánchez
- Research Group on Quality; Safety; and Bioactivity of Plant Foods; CEBAS-CSIC; Murcia Spain
| | - María V. Selma
- Research Group on Quality; Safety; and Bioactivity of Plant Foods; CEBAS-CSIC; Murcia Spain
| | - María T. García-Conesa
- Research Group on Quality; Safety; and Bioactivity of Plant Foods; CEBAS-CSIC; Murcia Spain
| | - Juan Carlos Espín
- Research Group on Quality; Safety; and Bioactivity of Plant Foods; CEBAS-CSIC; Murcia Spain
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47
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Kang I, Kim Y, Tomás-Barberán FA, Espín JC, Chung S. Urolithin A, C, and D, but not iso-urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes. Mol Nutr Food Res 2016; 60:1129-38. [DOI: 10.1002/mnfr.201500796] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 01/30/2016] [Accepted: 02/03/2016] [Indexed: 11/09/2022]
Affiliation(s)
- Inhae Kang
- Department of Nutrition and Health Sciences; University of Nebraska-Lincoln; Lincoln NE, USA
| | - YongEun Kim
- Department of Nutrition and Health Sciences; University of Nebraska-Lincoln; Lincoln NE, USA
| | | | | | - Soonkyu Chung
- Department of Nutrition and Health Sciences; University of Nebraska-Lincoln; Lincoln NE, USA
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Núñez-Sánchez MÁ, Karmokar A, González-Sarrías A, García-Villalba R, Tomás-Barberán FA, García-Conesa MT, Brown K, Espín JC. In vivo relevant mixed urolithins and ellagic acid inhibit phenotypic and molecular colon cancer stem cell features: A new potentiality for ellagitannin metabolites against cancer. Food Chem Toxicol 2016; 92:8-16. [PMID: 26995228 DOI: 10.1016/j.fct.2016.03.011] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 03/11/2016] [Accepted: 03/14/2016] [Indexed: 12/26/2022]
Abstract
Colon cancer stem cells (CSCs) offer a novel paradigm for colorectal cancer (CRC) treatment and dietary polyphenols may contribute to battle these cells. Specifically, polyphenol-derived colon metabolites have the potential to interact with and affect colon CSCs. We herein report the effects against colon CSCs of two mixtures of ellagitannin (ET) metabolites, ellagic acid (EA) and the gut microbiota-derived urolithins (Uro) at concentrations detected in the human colon tissues following the intake of ET-containing products (pomegranate, walnuts). These mixtures reduce phenotypic and molecular features in two models of colon CSCs: Caco-2 cells and primary tumour cells from a patient with CRC. The mixture containing mostly Uro-A (85% Uro-A, 10% Uro-C, 5% EA) was most effective at inhibiting the number and size of colonospheres and aldehyde dehydrogenase activity (ALDH, a marker of chemoresistance) whereas the mixture containing less Uro-A but IsoUro-A and Uro-B (30% Uro-A, 50% IsoUro-A, 10% Uro-B, 5% Uro-C, 5% EA) had some effects on the number and size of colonospheres but not on ALDH. These data support a role for polyphenols metabolites in the control of colon cancer chemoresistance and relapse and encourage the research on the effects of polyphenols against CSCs.
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Affiliation(s)
- María Ángeles Núñez-Sánchez
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
| | - Ankur Karmokar
- Cancer Chemoprevention Group, Department of Cancer Studies, University of Leicester, Leicester, UK
| | - Antonio González-Sarrías
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
| | - Rocío García-Villalba
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
| | - Francisco A Tomás-Barberán
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
| | - María Teresa García-Conesa
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
| | - Karen Brown
- Cancer Chemoprevention Group, Department of Cancer Studies, University of Leicester, Leicester, UK
| | - Juan Carlos Espín
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
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Afrin S, Giampieri F, Gasparrini M, Forbes-Hernandez TY, Varela-López A, Quiles JL, Mezzetti B, Battino M. Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment. Molecules 2016; 21:169. [PMID: 26840292 PMCID: PMC6273426 DOI: 10.3390/molecules21020169] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Revised: 01/22/2016] [Accepted: 01/26/2016] [Indexed: 12/15/2022] Open
Abstract
Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer.
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Affiliation(s)
- Sadia Afrin
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Francesca Giampieri
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Massimiliano Gasparrini
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Tamara Y Forbes-Hernandez
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
| | - Alfonso Varela-López
- Department of Physiology, Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada, Armilla, Avda. del Conocimiento s.n., Armilla 18100, Spain.
| | - José L Quiles
- Department of Physiology, Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada, Armilla, Avda. del Conocimiento s.n., Armilla 18100, Spain.
| | - Bruno Mezzetti
- Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Università Politecnica delle Marche, Via Ranieri 65, Ancona 60131, Italy.
| | - Maurizio Battino
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy.
- Centre for Nutrition & Health, Universidad Europea del Atlantico (UEA), Santander 39011, Spain.
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50
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González-Sarrías A, Núñez-Sánchez MÁ, Tomé-Carneiro J, Tomás-Barberán FA, García-Conesa MT, Espín JC. Comprehensive characterization of the effects of ellagic acid and urolithins on colorectal cancer and key-associated molecular hallmarks: MicroRNA cell specific induction of CDKN1A (p21) as a common mechanism involved. Mol Nutr Food Res 2015; 60:701-16. [PMID: 26634414 DOI: 10.1002/mnfr.201500780] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 11/25/2015] [Accepted: 11/29/2015] [Indexed: 12/14/2022]
Abstract
SCOPE Ellagitannins, ellagic acid, and the colonic metabolites urolithins (Uros) exhibit anticancer effects against colon cells, but a comprehensive molecular analysis has not been done. Herein, we used a panel of cell lines to first time evaluate the antiproliferative properties and accompanying molecular responses of two ellagitannin metabolites mixtures mimicking the situation in vivo and of each individual metabolite. METHODS AND RESULTS We examined cell growth, cell cycle, apoptosis, and the expression of related genes and microRNAs (miRs) in a panel of nonmalignant and malignant colon cell lines. Regardless of the composition, the mixed metabolites similarly inhibited proliferation, induced cycle arrest, and apoptosis. All the metabolites contributed to these effects, but Uro-A, isourolithin A, Uro-C, and Uro-D were more potent than Uro-B and ellagic acid. Despite molecular differences between the cell lines, we discerned relevant changes in key cancer markers and corroborated the induction of CDKN1A (cyclin-dependent kinase inhibitor 1A gene (p21, Cip1); encoding p21) as a common step underlying the anticancer properties of Uros. Interestingly, cell-unique downregulation of miR-224 or upregulation of miR-215 was found associated with CDKN1A induction. CONCLUSION Physiologically relevant mixtures of Uros exert anticancer effects against colon cancer cells via a common CDKN1A upregulatory mechanism. Other associated molecular responses are however heterogeneous and mostly cell-specific.
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Affiliation(s)
- Antonio González-Sarrías
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - María Ángeles Núñez-Sánchez
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Joao Tomé-Carneiro
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Francisco A Tomás-Barberán
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - María Teresa García-Conesa
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Juan Carlos Espín
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
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