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Bernabeu M, Gharibzahedi SMT, Ganaie AA, Macha MA, Dar BN, Castagnini JM, Garcia-Bonillo C, Meléndez-Martínez AJ, Altintas Z, Barba FJ. The potential modulation of gut microbiota and oxidative stress by dietary carotenoid pigments. Crit Rev Food Sci Nutr 2023; 64:12555-12573. [PMID: 37691412 DOI: 10.1080/10408398.2023.2254383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Gut microbiota plays a crucial role in regulating the response to immune checkpoint therapy, therefore modulation of the microbiome with bioactive molecules like carotenoids might be a very effective strategy to reduce the risk of chronic diseases. This review highlights the bio-functional effect of carotenoids on Gut Microbiota modulation based on a bibliographic search of the different databases. The methodology given in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) has been employed for developing this review using papers published over two decades considering keywords related to carotenoids and gut microbiota. Moreover, studies related to the health-promoting properties of carotenoids and their utilization in the modulation of gut microbiota have been presented. Results showed that there can be quantitative changes in intestinal bacteria as a function of the type of carotenoid. Due to the dependency on several factors, gut microbiota continues to be a broad and complex study subject. Carotenoids are promising in the modulation of Gut Microbiota, which favored the appearance of beneficial bacteria, resulting in the protection of villi and intestinal permeability. In conclusion, it can be stated that carotenoids may help to protect the integrity of the intestinal epithelium from pathogens and activate immune cells.
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Affiliation(s)
- Manuel Bernabeu
- Research Group in Innovative Technologies for Sustainable Food (ALISOST), Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda, Burjassot, Burjassot, València, Spain
- Vicerectorat de Recerca, Universitat de Barcelona (UB), Barcelona, Spain
| | - Seyed Mohammad Taghi Gharibzahedi
- Faculty of Natural Sciences and Maths, Institute of Chemistry, Technical University of Berlin, Berlin, Germany
- Faculty of Engineering, Institute of Materials Science, Kiel University, Kiel, Germany
| | - Arsheed A Ganaie
- Watson Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
| | - Muzafar A Macha
- Watson Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Kashmir, India
| | - Basharat N Dar
- Department of Food Technology, Islamic University of Science and Technology, Kashmir, India
| | - Juan M Castagnini
- Research Group in Innovative Technologies for Sustainable Food (ALISOST), Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda, Burjassot, Burjassot, València, Spain
| | | | | | - Zeynep Altintas
- Faculty of Natural Sciences and Maths, Institute of Chemistry, Technical University of Berlin, Berlin, Germany
- Faculty of Engineering, Institute of Materials Science, Kiel University, Kiel, Germany
| | - Francisco J Barba
- Research Group in Innovative Technologies for Sustainable Food (ALISOST), Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda, Burjassot, Burjassot, València, Spain
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Liang Z, Xu Y, Zhang Y, Zhang X, Song J, Qian H, Jin J. Anticancer applications of phytochemicals in gastric cancer: Effects and molecular mechanism. Front Pharmacol 2023; 13:1078090. [PMID: 36712679 PMCID: PMC9877357 DOI: 10.3389/fphar.2022.1078090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/28/2022] [Indexed: 01/15/2023] Open
Abstract
Gastric cancer (GC) is the fourth most common malignant cancer and is a life-threatening disease worldwide. Phytochemicals have been shown to be a rational, safe, non-toxic, and very promising approach to the prevention and treatment of cancer. It has been found that phytochemicals have protective effects against GC through inhibiting cell proliferation, inducing apoptosis and autophagy, suppressing cell invasion and migration, anti-angiogenesis, inhibit Helicobacter pylori infection, regulating the microenvironment. In recent years, the role of phytochemicals in the occurrence, development, drug resistance and prognosis of GC has attracted more and more attention. In order to better understand the relationship between phytochemicals and gastric cancer, we briefly summarize the roles and functions of phytochemicals in GC tumorigenesis, development and prognosis. This review will probably help guide the public to prevent the occurrence and development of GC through phytochemicals, and develop functional foods or drugs for the prevention and treatment of gastric cancer.
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Affiliation(s)
- Zhaofeng Liang
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Chang Zhou, China
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yumeng Xu
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yue Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Xinyi Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jiajia Song
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Hui Qian
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Chang Zhou, China
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jianhua Jin
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Chang Zhou, China
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Srivastava S, Dubey AK, Madaan R, Bala R, Gupta Y, Dhiman BS, Kumar S. Emergence of nutrigenomics and dietary components as a complementary therapy in cancer prevention. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:89853-89873. [PMID: 36367649 DOI: 10.1007/s11356-022-24045-x] [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: 04/23/2022] [Accepted: 11/02/2022] [Indexed: 06/16/2023]
Abstract
Cancer is an illness characterized by abnormal cell development and the capability to infiltrate or spread to rest of the body. A tumor is the term for this abnormal growth that develops in solid tissues like an organ, muscle, or bone and can spread to other parts of the body through the blood and lymphatic systems. Nutrition is a critical and immortal environmental component in the development of all living organisms encoding the relationship between a person's nutrition and their genes. Nutrients have the ability to modify gene expression and persuade alterations in DNA and protein molecules which is researched scientifically in nutrigenomics. These interactions have a significant impact on the pharmacokinetic properties of bioactive dietary components as well as their site of action/molecular targets. Nutrigenomics encompasses nutrigenetics, epigenetics, and transcriptomics as well as other "omic" disciplines like proteomics and metabolomics to explain the vast disparities in cancer risk among people with roughly similar life style. Clinical trials and researches have evidenced that alternation of dietary habits is potentially one of the key approaches for reducing cancer risk in an individual. In this article, we will target how nutrigenomics and functional food work as preventive therapy in reducing the risk of cancer.
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Affiliation(s)
| | - Ankit Kumar Dubey
- Institute of Scholars, Bengaluru, 577102, Karnataka, India.
- iGlobal Research and Publishing Foundation, New Delhi, 110059, India.
| | - Reecha Madaan
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Rajni Bala
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Yugam Gupta
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | | | - Suresh Kumar
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, Punjab, India
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Mitra S, Emran TB, Chandran D, Zidan BMRM, Das R, Mamada SS, Masyita A, Salampe M, Nainu F, Khandaker MU, Idris AM, Simal-Gandara J. Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers. Front Nutr 2022; 9:951935. [PMID: 35990357 PMCID: PMC9386315 DOI: 10.3389/fnut.2022.951935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 07/12/2022] [Indexed: 11/23/2022] Open
Abstract
In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the “guardian of the genome,” the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. This review discusses the functional foods bioactive compounds derived from several cruciferous vegetables and their use in altering the tumor-suppressive effect of p53 proteins. The association between the mutation of p53 and the incidence of gastrointestinal malignancies (gastric, small intestine, colon, liver, and pancreatic cancers) is also discussed. This review contains crucial information about the use of cruciferous vegetables in the treatment of gastrointestinal tract malignancies.
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Affiliation(s)
- Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh.,Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore, Tamil Nadu, India
| | | | - Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | | | - Ayu Masyita
- Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia
| | | | - Firzan Nainu
- Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Subang Jaya, Selangor, Malaysia
| | - Abubakr M Idris
- Department of Chemistry, College of Science, King Khalid University, Abha, Saudi Arabia.,Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, Universidade de Vigo, Ourense, Spain
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β-Carotene Attenuates Apoptosis and Autophagy via PI3K/AKT/mTOR Signaling Pathway in Necrotizing Enterocolitis Model Cells IEC-6. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2502263. [PMID: 35754683 PMCID: PMC9232345 DOI: 10.1155/2022/2502263] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 05/26/2022] [Indexed: 12/03/2022]
Abstract
Background Necrotizing enterocolitis (NEC) is a devastating disease affecting the gastrointestinal tract in the newborn period. In recent years, the role of apoptosis and autophagy in intestinal mucosal barrier dysfunction has come into prominence in research regarding the pathogenesis of NEC. β-Carotene is a well-known vitamin A precursor, and its content in breast milk is relatively high, especially in the colostrum. In the present study, we investigated the protective effect of β-carotene on necrotizing enterocolitis model cells IEC-6 induced by lipopolysaccharide (LPS). Methods CCK-8 assay was performed to evaluate cell viability. The Annexin V-FITC/PI method was used to detect apoptosis. Western blotting was utilized to measure the expression levels of proteins. Immunofluorescence analysis was used to assess the autophagy of IEC-6 cells. Results Our findings indicated that β-carotene inhibited the apoptosis of IEC-6 cells by downregulating cleaved caspase-3 levels and Bax levels and upregulating Bcl-2 levels, reducing cell autophagy via downregulating LC3II/I ratio and upregulating p62 levels. In addition, the expression of p-PI3K, p-AKT, and p-mTOR was upregulated after β-carotene treatment. Interestingly, these changes induced by β-carotene were partially reversed by rapamycin and voxtalisib. Conclusion In conclusion, our findings indicated that β-carotene can attenuate apoptosis and autophagy of IEC-6 cells induced by LPS via activating the PI3K/AKT/mTOR signaling pathway. Therefore, β-carotene may be a promising drug used in the clinical treatment of NEC.
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Agrimonia pilosa: A Phytochemical and Pharmacological Review. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3742208. [PMID: 35529922 PMCID: PMC9076299 DOI: 10.1155/2022/3742208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 03/20/2022] [Accepted: 03/31/2022] [Indexed: 12/02/2022]
Abstract
Agrimonia pilosa Ledeb., which belongs to Agrimonia and Rosaceae, is used in traditional Chinese medicine. It exhibits excellent medicinal properties and has been used to treat various diseases, such as tumors, trichomoniasis, vaginitis, diarrhea, and dysentery. Phytochemical studies have revealed that Agrimonia has over 100 secondary metabolites that can be categorized into six classes, i.e., flavonoids, isocoumarins, triterpenes, phloroglucinol derivatives, tannins, and organic acids. This review summarizes recently published literature on the chemical structures of 90 bioactive compounds that have been identified in A. pilosa and examines their pharmacological properties, including their antitumor, anti-inflammatory, antioxidant, antibacterial, and antidiabetic properties, as well as the potential development of parasitic resistance to these chemicals. This review highlights existing knowledge gap and serves as a basis for developing novel preparations of A. pilosa with medicinal value.
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Chen QH, Wu BK, Pan D, Sang LX, Chang B. Beta-carotene and its protective effect on gastric cancer. World J Clin Cases 2021; 9:6591-6607. [PMID: 34447808 PMCID: PMC8362528 DOI: 10.12998/wjcc.v9.i23.6591] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 05/16/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Beta-carotene is an important natural pigment that is very beneficial to human health. It is widely found in vegetables and fruits. The three main functions are antioxidant effects, cell gap junction-related functions and immune-related functions. Because of its diverse functions, beta-carotene is believed to prevent and treat many chronic diseases. Gastric cancer is one of the most important diseases it can treat. Gastric cancer is a type of cancer with a high incidence. Its etiology varies, and the pathogenesis is complex. Gastric cancer seriously affects human health. The role of beta-carotene, a natural nutrient, in gastric cancer has been explored by many researchers, including molecular mechanisms and epidemiological studies. Molecular studies have mainly focused on oxidative stress, cell cycle, signal transduction pathways and immune-related mechanisms of beta-carotene in gastric cancer. Many epidemiological surveys and cohort studies of patients with gastric cancer have been conducted, and the results of these epidemiological studies vary due to the use of different research methods and analysis of different regions. This paper will summarize the results of these studies, mainly in terms of molecular mechanisms and epidemiological research results, which will provide a systematic basis for future studies of the treatment and prognosis of gastric cancer. This paper will help researchers identify new research directions.
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Affiliation(s)
- Qian-Hui Chen
- Department of Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bao-Kang Wu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Chopra B, Dhingra AK. Natural products: A lead for drug discovery and development. Phytother Res 2021; 35:4660-4702. [PMID: 33847440 DOI: 10.1002/ptr.7099] [Citation(s) in RCA: 158] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 03/01/2021] [Accepted: 03/09/2021] [Indexed: 12/29/2022]
Abstract
Natural products are used since ancient times in folklore for the treatment of various ailments. Plant-derived products have been recognized for many years as a source of therapeutic agents and structural diversity. A literature survey has been carried out to determine the utility of natural molecules and their modified analogs or derivatives as pharmacological active entities. This review presents a study on the importance of natural products in terms of drug discovery and development. It describes how the natural components can be utilized after small modifications in new perspectives. Various new modifications in structure offer a unique opportunity to establish a new molecular entity with better pharmacological potential. It was concluded that in this current era, new attempts are taken to utilize the compounds derived from natural sources as novel drug candidates, with a focus to find and discover new effective molecules that were referred to as "new entities of natural product drug discovery."
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Affiliation(s)
- Bhawna Chopra
- Department of Pharmaceutical Chemistry, Guru Gobind Singh College of Pharmacy, Yamuna Nagar, India
| | - Ashwani Kumar Dhingra
- Department of Pharmaceutical Chemistry, Guru Gobind Singh College of Pharmacy, Yamuna Nagar, India
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β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in Helicobacter pylori-Infected Gastric Epithelial Cells. Molecules 2021; 26:molecules26061567. [PMID: 33809289 PMCID: PMC8002206 DOI: 10.3390/molecules26061567] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/02/2021] [Accepted: 03/10/2021] [Indexed: 02/08/2023] Open
Abstract
Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with H. pylori, a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by H. pylori infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits H. pylori-induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that H. pylori induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed H. pylori-induced MMP-10 expression, suggesting that H. pylori induces MMP-10 expression through MAPKs. β-Carotene inhibited the H. pylori-induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in H. pylori-infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in H. pylori-infected gastric epithelial cells.
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Lakey-Beitia J, Vasquez V, Mojica-Flores R, Fuentes C AL, Murillo E, Hedge ML, Rao KS. Pouteria sapota (Red Mamey Fruit): Chemistry and Biological Activity of Carotenoids. Comb Chem High Throughput Screen 2021; 25:1134-1147. [PMID: 33645478 DOI: 10.2174/1386207324666210301093711] [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: 10/30/2020] [Revised: 01/14/2021] [Accepted: 01/18/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Red mamey fruit known as P. sapota, comes from trees found in Mesoamerica and Asia. This fruit is considered a nutraceutical food due to it's a food and has multiple beneficial health including anti-amyloidogenic activity and potential anti-tumorigenic property. Red mamey fruit contain a variety of carotenoids including novel ketocarotenoids such as sapotexanthin and cryptocapsin. A ketocarotenoid is a chemical compound with a carbonyl group present in the β-ring or in the double bond chain of a carotenoid. In red mamey, the 3'-deoxy-k-end group in sapotexanthin has proved to be an important pro-vitamin A source, which is essential for maintaining a healthy vision and cognitive processes. OBJECTIVE Summarize the chemistry and biological activity of the studied carotenoids present in this fruit until now. METHOD An exhaustive extraction is the most usual methodology to isolate and thoroughly characterize the carotenoids present in this fruit. High performance liquid chromatography is used to determine the profile of total carotenoid and its purity. Atmospheric pressure chemical ionization is used to determine the molecular weight of carotenoid. Nuclear magnetic resonance is used to determine the structure of carotenoids. RESULT For each 100 g of fresh weight, 0.12 mg of total carotenoid from this fruit can be obtained. Out of the more than 47 reported carotenoids in red mamey, only 34 have a detailed characterization. CONCLUSION it is important to continue studying the chemical composition and biological activity of this unique tropical fruit with commercial and nutritional value.
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Affiliation(s)
- Johant Lakey-Beitia
- Centre for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103. Panama
| | - Velmarini Vasquez
- Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103. Panama
| | - Randy Mojica-Flores
- Centre for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103. Panama
| | - Arelys L Fuentes C
- Centre for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103. Panama
| | - Enrique Murillo
- Department of Biochemistry, Faculty of Exact Natural Sciences and Technology, University of Panama, Panama City. Panama
| | - Muralidhar L Hedge
- Department of Neurosurgery, Houston Methodist Research Institute, Houston, Texas, 77030. United States
| | - K S Rao
- Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103. Panama
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Kuznietsova I, Khomychak I, Petrova J, Haibin Y, Yarmolyuk M, Tkachenko S. THE USE OF TOMATO POWDER IN PRODUCTION OF MAYONNAISE. FOOD SCIENCE AND TECHNOLOGY 2020. [DOI: 10.15673/fst.v14i4.1917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
It has been studied how tomato powder can be used in the production of mayonnaise. The content of essential amino acids in tomato powder has been compared with the FAO/WHO norms. Fresh plum tomatoes contain 0.158g of non-essential amino acids (in terms of 100g of dry matter), which covers 4.37% of the body’s requirements according to the standardised values approved by FAO/WHO. Tomato powder contains 0.14g of non-essential amino acids. The amount of essential amino acids in fresh tomatoes is 0.216g per 100g, and in powder, it is 0.181g per 100g. The amino acids that determine the intensity of sweetness have been established to amount to 0.165g in 100g of fresh tomatoes and to 0.116g in 100g of powder. So, in the course of drying, the product’s taste qualities related to feeling sweetness are reduced. It has been determined that the organoleptic properties of a product can be improved by adding tomato powder in the amount 1.8–2.2% and using a blend of oils. The mayonnaise samples obtained were cream-coloured with red particles of tomato powder. The samples had a soft structure and a more uniform and viscous texture than the control sample. The microscopic method has shown the homogeneous consistency of the product obtained. It has been noted that the absence of structure-forming agents does not reduce the quality indicators and does not impair the consistency of the finished product. According to the organoleptic parameters, the dose of tomato powder has been determined, which improves the taste of mayonnaise and does not make it oversweet. The research results show the prospects of using tomato powder not only as a carotene-containing raw material, but also as a raw material with a high content of amino acids. Besides, the use of tomato powder can modify the taste of such a product as mayonnaise.
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Erden Y. Capsanthin Stimulates the Mitochondrial Apoptosis-Mediated Cell Death, following DNA Damage in MCF-7 Cells. Nutr Cancer 2020; 73:662-670. [PMID: 32933334 DOI: 10.1080/01635581.2020.1819347] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Carotenoids found in fruits and vegetables are compounds with significant biological activities. Epidemiological studies report that these compounds have significant anticancer effects, as well reducing the risk of cancer. In the present study, we aimed to determine the effects of capsanthin, an important carotenoid of paprika, on expressions of proteins playing roles in the mitochondrial apoptosis pathway, in addition to its possible cytotoxic and genotoxic effects in MCF-7 cells. Furthermore, possible oxidant/anti-oxidant roles of capsanthin on MCF-7 cells were investigated. The viability of MCF-7 cells was significantly decreased after 24 h of capsanthin application. After Comet analysis, it was determined that the capsanthin caused DNA damage on a dose-dependent manner. Furthermore, Western blot analysis showed that capsanthin application increased p53 and Bax protein expressions and caused a decrease in Bcl-2 protein level. Capsanthin treatment decreased catalase and glutathione levels but increased lipid peroxidation. These results show that the capsanthin causes oxidative stress and DNA damage, and increases mitochondrial apoptotic mechanism-mediated cell death after p53 and Bax protein activations.
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Affiliation(s)
- Yavuz Erden
- Department of Molecular Biology and Genetics, Faculty of Science, Bartin University, Bartin, Turkey
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Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5103272. [PMID: 32855967 PMCID: PMC7443216 DOI: 10.1155/2020/5103272] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/18/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022]
Abstract
Human gastric cancer is one of the most common malignant tumors with a poor prognosis. Cisplatin (CDDP) is a well-known first-line chemotherapeutic drug. Acquired resistance retards the clinical application of CDDP in gastric cancer. In this study, circular RNA circ_0026359 was demonstrated to be overexpressed in gastric cancer tissues/cells compared with normal gastric tissues/cells and was overexpressed in CDDP-resistant gastric cancer tissues/cells compared with CDDP-sensitive gastric cancer tissues/cells. High levels of circ_0026359 were associated with low overall survival (OS) and relapse-free survival (RFS) rates in gastric cancer patients. circ_0026359 was examined to promote CDDP resistance in gastric cancer cells. circ_0026359 directly interacted and negatively regulated miR-1200. POLD4 was a direct target of miR-1200. miR-1200/POLD4 pathway mediated the promoting role of circ_0026359 in CDDP resistance of gastric cancer. circ_0026359 could be used as a potential target for CDDP-resistant gastric cancer therapy.
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Shin J, Song MH, Oh JW, Keum YS, Saini RK. Pro-Oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence. Antioxidants (Basel) 2020; 9:E532. [PMID: 32560478 PMCID: PMC7346220 DOI: 10.3390/antiox9060532] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 06/15/2020] [Accepted: 06/15/2020] [Indexed: 12/15/2022] Open
Abstract
Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.
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Affiliation(s)
- Juhyun Shin
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea; (J.S.); (J.-W.O.)
| | - Min-Ho Song
- Department of Crop Science, Konkuk University, Seoul 143-701, Korea; (M.-H.S.); (Y.-S.K.)
| | - Jae-Wook Oh
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea; (J.S.); (J.-W.O.)
| | - Young-Soo Keum
- Department of Crop Science, Konkuk University, Seoul 143-701, Korea; (M.-H.S.); (Y.-S.K.)
| | - Ramesh Kumar Saini
- Department of Crop Science, Konkuk University, Seoul 143-701, Korea; (M.-H.S.); (Y.-S.K.)
- Institute of Natural Science and Agriculture, Konkuk University, Seoul 143-701, Korea
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Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol 2017; 174:1290-1324. [PMID: 27638711 PMCID: PMC5429337 DOI: 10.1111/bph.13625] [Citation(s) in RCA: 426] [Impact Index Per Article: 53.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 08/21/2016] [Accepted: 08/31/2016] [Indexed: 01/06/2023] Open
Abstract
Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. LINKED ARTICLES This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
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Affiliation(s)
- Alireza Milani
- Department of Hepatitis and AIDSPasteur Institute of IranTehranIran
| | | | - Sepideh Shahbazi
- Department of Hepatitis and AIDSPasteur Institute of IranTehranIran
| | - Azam Bolhassani
- Department of Hepatitis and AIDSPasteur Institute of IranTehranIran
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Naz H, Khan P, Tarique M, Rahman S, Meena A, Ahamad S, Luqman S, Islam A, Ahmad F, Hassan MI. Binding studies and biological evaluation of β-carotene as a potential inhibitor of human calcium/calmodulin-dependent protein kinase IV. Int J Biol Macromol 2016; 96:161-170. [PMID: 27956097 DOI: 10.1016/j.ijbiomac.2016.12.024] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 12/02/2016] [Accepted: 12/04/2016] [Indexed: 12/27/2022]
Abstract
Human calcium/calmodulin-dependent protein kinase IV (CAMKIV), a member of Ser/Thr kinase family, is associated with cancer, cerebral hypoxia and neurodegenerative diseases. β-carotene is a colored organic compound, abundant in plants and fruits and is used in cancer prevention. Here, we report a strong binding affinity of β-carotene with CAMKIV using molecular docking, fluorescence binding and isothermal titration calorimetry methods. Furthermore, β-carotene also reduces the enzyme activity of CAMKIV moderately as observed during ATPase assay. To see the role of β-carotene on cell proliferation and apoptosis, cancerous cells (HeLa, HuH7and MCF-7) and normal (HEK-293-T) cell lines were used. Admirable anticancer activity of β-carotene was observed. We further performed propidium iodide and DAPI (4',6-diamidino-2-phenylindole) assays to understand the mechanism of anticancer activity of β-carotene at molecular level. Our findings provide a newer insight into the use of β-carotene in cancer prevention and protection via inhibition of CAMKIV by regulating the signaling pathways.
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Affiliation(s)
- Huma Naz
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Parvez Khan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Mohd Tarique
- Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India
| | - Safikur Rahman
- Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 712-749, South Korea
| | - Abha Meena
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India
| | - Shahzaib Ahamad
- Department of Biotechnology, College of Engineering & Technology, IFTM University, Lodhipur-Rajput, Delhi Road, Moradabad, India
| | - Suaib Luqman
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Faizan Ahmad
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
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Ferguson LR, Chen H, Collins AR, Connell M, Damia G, Dasgupta S, Malhotra M, Meeker AK, Amedei A, Amin A, Ashraf SS, Aquilano K, Azmi AS, Bhakta D, Bilsland A, Boosani CS, Chen S, Ciriolo MR, Fujii H, Guha G, Halicka D, Helferich WG, Keith WN, Mohammed SI, Niccolai E, Yang X, Honoki K, Parslow VR, Prakash S, Rezazadeh S, Shackelford RE, Sidransky D, Tran PT, Yang ES, Maxwell CA. Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Semin Cancer Biol 2015; 35 Suppl:S5-S24. [PMID: 25869442 PMCID: PMC4600419 DOI: 10.1016/j.semcancer.2015.03.005] [Citation(s) in RCA: 202] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 03/08/2015] [Accepted: 03/13/2015] [Indexed: 02/06/2023]
Abstract
Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology.
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Affiliation(s)
| | - Helen Chen
- Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada
| | - Andrew R Collins
- Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Marisa Connell
- Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada
| | - Giovanna Damia
- Department of Oncology, Instituti di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - Santanu Dasgupta
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, United States
| | | | - Alan K Meeker
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Amr Amin
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates; Faculty of Science, Cairo University, Cairo, Egypt
| | - S Salman Ashraf
- Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Katia Aquilano
- Department of Biology, Università di Roma Tor Vergata, Rome, Italy
| | - Asfar S Azmi
- Department of Biology, University of Rochester, Rochester, United States
| | - Dipita Bhakta
- School of Chemical and BioTechnology, SASTRA University, Thanjavur, Tamil Nadu, India
| | - Alan Bilsland
- Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Chandra S Boosani
- Department of BioMedical Sciences, Creighton University, Omaha, NE, United States
| | - Sophie Chen
- Department of Research & Development, Ovarian and Prostate Cancer Research Trust Laboratory, Guildford, Surrey, United Kingdom
| | | | - Hiromasa Fujii
- Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Gunjan Guha
- School of Chemical and BioTechnology, SASTRA University, Thanjavur, Tamil Nadu, India
| | | | - William G Helferich
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - W Nicol Keith
- Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Sulma I Mohammed
- Department of Comparative Pathobiology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, United States
| | - Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Xujuan Yang
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Kanya Honoki
- Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan
| | | | - Satya Prakash
- School of Pharmacy, University College Cork, Cork, Ireland
| | - Sarallah Rezazadeh
- Department of Biology, University of Rochester, Rochester, United States
| | - Rodney E Shackelford
- Department of Pathology, Louisiana State University Health Shreveport, Shreveport, LA, United States
| | - David Sidransky
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Phuoc T Tran
- Departments of Radiation Oncology & Molecular Radiation Sciences, Oncology and Urology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Eddy S Yang
- Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, United States
| | - Christopher A Maxwell
- Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada.
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Lee YM, Kim MJ, Kim Y, Kim H. Glutamine Deprivation Causes Hydrogen Peroxide-induced Interleukin-8 Expression via Jak1/Stat3 Activation in Gastric Epithelial AGS Cells. J Cancer Prev 2015; 20:179-84. [PMID: 26473156 PMCID: PMC4597806 DOI: 10.15430/jcp.2015.20.3.179] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND The Janus kinase (Jak)/Signal transducers of activated transcription (Stat) pathway is an upstream signaling pathway for NF-κB activation in Helicobacter pylori-induced interleukin (IL)-8 production in gastric epithelial AGS cells. H. pylori activates NADPH oxidase and produces hydrogen peroxide, which activates Jak1/Stat3 in AGS cells. Therefore, hydrogen peroxide may be critical for IL-8 production via Jak/Stat activation in gastric epithelial cells. Glutamine is depleted during severe injury and stress and contributes to the formation of glutathione (GSH), which is involved in conversion of hydrogen peroxide into water as a cofactor for GSH peroxidase. METHODS We investigated whether glutamine deprivation induces hydrogen peroxide-mediated IL-8 production and whether hydrogen peroxide activates Jak1/Stat3 to induce IL-8 in AGS cells. Cells were cultured in the presence or absence of glutamine or hydrogen peroxide, with or without GSH or a the Jak/Stat specific inhibitor AG490. RESULTS Glutamine deprivation decreased GSH levels, but increased levels of hydrogen peroxide and IL-8, an effect that was inhibited by treatment with GSH. Hydrogen peroxide induced the activation of Jak1/Stat3 time-dependently. AG490 suppressed hydrogen peroxide- induced activation of Jak1/Stat3 and IL-8 expression in AGS cells, but did not affect levels of reactive oxygen species in AGS cells. CONCLUSIONS In gastric epithelial AGS cells, glutamine deprivation increases hydrogen peroxide levels and IL-8 expression, which may be mediated by Jak1/Stat3 activation. Glutamine supplementation may be beneficial for preventing gastric inflammation by suppressing hydrogen peroxide-mediated Jak1/Stat3 activation and therefore, reducing IL-8 production. Scavenging hydrogen peroxide or targeting Jak1/Stat3 may also prevent oxidant-mediated gastric inflammation.
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Affiliation(s)
- Yun Mi Lee
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Mi Jung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Youngha Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
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Alternative and efficient extraction methods for marine-derived compounds. Mar Drugs 2015; 13:3182-230. [PMID: 26006714 PMCID: PMC4446625 DOI: 10.3390/md13053182] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 05/01/2015] [Accepted: 05/06/2015] [Indexed: 12/21/2022] Open
Abstract
Marine ecosystems cover more than 70% of the globe’s surface. These habitats are occupied by a great diversity of marine organisms that produce highly structural diverse metabolites as a defense mechanism. In the last decades, these metabolites have been extracted and isolated in order to test them in different bioassays and assess their potential to fight human diseases. Since traditional extraction techniques are both solvent- and time-consuming, this review emphasizes alternative extraction techniques, such as supercritical fluid extraction, pressurized solvent extraction, microwave-assisted extraction, ultrasound-assisted extraction, pulsed electric field-assisted extraction, enzyme-assisted extraction, and extraction with switchable solvents and ionic liquids, applied in the search for marine compounds. Only studies published in the 21st century are considered.
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Park Y, Choi J, Lim JW, Kim H. β-Carotene-induced apoptosis is mediated with loss of Ku proteins in gastric cancer AGS cells. GENES AND NUTRITION 2015; 10:467. [PMID: 25981694 DOI: 10.1007/s12263-015-0467-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Accepted: 05/02/2015] [Indexed: 12/18/2022]
Abstract
High dietary intakes and high blood levels of β-carotene are associated with a decreased incidence of various cancers. The anticancer effect of β-carotene is related to its pro-oxidant activity. DNA repair Ku proteins, as a heterodimer of Ku70 and Ku80, play a crucial role in DNA double-strand break repair. Reductions in Ku70/80 contribute to apoptosis. Previously, we showed that reactive oxygen species (ROS) activate caspase-3 which induces degradation of Ku proteins. In the present study, we investigated the mechanism of β-carotene-induced apoptosis of gastric cancer AGS cells by determining cell viability, DNA fragmentation, apoptotic indices (increases in cytochrome c and Bax, decrease in Bcl-2), ROS levels, mitochondrial membrane potential, caspase-3 activity, Ku70/80 levels, and Ku-DNA-binding activity of the cells treated with or without antioxidant N-acetyl cysteine and caspase-3 inhibitor z-DEVED-fmk. As a result, β-carotene induced apoptosis (decrease in cell viability, increases in DNA fragmentation and apoptotic indices) and caspase-3 activation, but decreased Ku70/80 levels and Ku-DNA-binding activity. β-Carotene-induced alterations (increase in caspase-3 activity, decrease in Ku proteins) and apoptosis were inhibited by N-acetyl cysteine and z-DEVED-fmk. Increment of intracellular and mitochondrial ROS levels and loss of mitochondrial membrane potential were suppressed by N-acetyl cysteine, but not by z-DEVED-fmk in β-carotene-treated cells. Therefore, β-carotene-induced increases in ROS and caspase-3 activity may lead to reduction of Ku70/80 levels, which results in apoptosis in gastric cancer cells. Loss of Ku proteins might be the underlying mechanism for β-carotene-induced apoptosis in gastric cancer cells.
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Affiliation(s)
- Yoona Park
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, 120-749, Korea
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Lim JY, Kim YS, Kim Y. β-carotene Regulates the Murine Liver Microenvironment of a Metastatic Neuroblastoma. J Cancer Prev 2014; 18:337-45. [PMID: 25337563 PMCID: PMC4189442 DOI: 10.15430/jcp.2013.18.4.337] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 12/19/2013] [Accepted: 12/19/2013] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND The anticarcinogenic effects of β-carotene (BC) have been well-characterized. However, the effect of BC on the microenvironment of a tumor remains to be investigated, especially since normal tissue proximal to a tumor has been shown to play a critical role in cancer progression and metastasis. For young children, neuroblastoma (NB) is the most common extracranial solid cancer diagnosed. Therefore, in the present study, effect of BC on the murine liver microenvironment of a metastatic NB was evaluated. METHODS USING A MOUSE MODEL, THREE EXPERIMENTAL GROUPS WERE ESTABLISHED: control mice, mice receiving an injection of SK-N-BE(2)C cells (TC), and mice receiving an injection of SK-N-BE(2)C cells plus 2 mg/kg BC twice a week (BC). Eight weeks after the injection of tumor, liver tissues were collected from all three groups, with the TC and BC tissues collected proximal to the metastatic NBs. RESULTS Compared to control tissues, BC tissues exhibited lower levels of proliferation, apoptosis, and metastasis. Assays for these processes included the detection of lower levels of proliferating cell nuclear antigen (PCNA), Bax, MMP2, and MMP9. In addition, higher levels of Bcl-2 were detected. Fewer cells undergoing an epithelial mesenchymal transition (EMT) were also observed in the BC group. Furthermore, BC tissues were associated with reduced expression of cancer stem cell marker, delta-like 1 homologue (DLK1), lower levels of VEGF mRNA and fewer CD31-positive cells. Finally, The antioxidant capability of the tumor microenvironment for the BC group was enhanced with higher expression levels of glutathione peroxidase (GPX), catalase, and manganese superoxide (MnSOD) detected. CONCLUSION These data suggest that BC affects the microenvironment of a tumor, and this enhances the anti-cancer effects of BC.
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Affiliation(s)
- Ji Ye Lim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea
| | - Yoo-Sun Kim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea
| | - Yuri Kim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea
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Effects of Mixed Micellar Lipids on Carotenoid Uptake by Human Intestinal Caco-2 Cells. Biosci Biotechnol Biochem 2014; 76:875-82. [DOI: 10.1271/bbb.110777] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts. Inflamm Res 2014; 63:347-56. [PMID: 24413629 DOI: 10.1007/s00011-013-0706-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 12/23/2013] [Accepted: 12/30/2013] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). MATERIALS We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. TREATMENT The cells were cultured with or without glutamine or GSH. METHODS ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. RESULTS While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and cultured without glutamine showed higher levels of ROS and IL-8 than those transfected with negative control siRNA; increased levels of ROS and IL-8 were suppressed by the treatment of glutamine. CONCLUSION Glutamine deprivation induces ROS production, NF-κB activation, and IL-8 expression as well as a reduction in GSH in A-T fibroblasts, all of which are attenuated by glutamine supplementation.
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Arigony ALV, de Oliveira IM, Machado M, Bordin DL, Bergter L, Prá D, Pêgas Henriques JA. The influence of micronutrients in cell culture: a reflection on viability and genomic stability. BIOMED RESEARCH INTERNATIONAL 2013; 2013:597282. [PMID: 23781504 PMCID: PMC3678455 DOI: 10.1155/2013/597282] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 04/23/2013] [Accepted: 05/03/2013] [Indexed: 12/31/2022]
Abstract
Micronutrients, including minerals and vitamins, are indispensable to DNA metabolic pathways and thus are as important for life as macronutrients. Without the proper nutrients, genomic instability compromises homeostasis, leading to chronic diseases and certain types of cancer. Cell-culture media try to mimic the in vivo environment, providing in vitro models used to infer cells' responses to different stimuli. This review summarizes and discusses studies of cell-culture supplementation with micronutrients that can increase cell viability and genomic stability, with a particular focus on previous in vitro experiments. In these studies, the cell-culture media include certain vitamins and minerals at concentrations not equal to the physiological levels. In many common culture media, the sole source of micronutrients is fetal bovine serum (FBS), which contributes to only 5-10% of the media composition. Minimal attention has been dedicated to FBS composition, micronutrients in cell cultures as a whole, or the influence of micronutrients on the viability and genetics of cultured cells. Further studies better evaluating micronutrients' roles at a molecular level and influence on the genomic stability of cells are still needed.
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Affiliation(s)
- Ana Lúcia Vargas Arigony
- Laboratório de Reparação de DNA em Eucariotos, Departamento de Biofísica/Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43422, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
| | - Iuri Marques de Oliveira
- Laboratório de Reparação de DNA em Eucariotos, Departamento de Biofísica/Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43422, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
| | - Miriana Machado
- Laboratório de Reparação de DNA em Eucariotos, Departamento de Biofísica/Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43422, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
- Instituto de Educação para Pesquisa, Desenvolvimento e Inovação Tecnológica—ROYAL, Unidade GENOTOX—ROYAL, Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43421, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
| | - Diana Lilian Bordin
- Laboratório de Reparação de DNA em Eucariotos, Departamento de Biofísica/Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43422, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
| | - Lothar Bergter
- Instituto de Educação para Pesquisa, Desenvolvimento e Inovação Tecnológica—ROYAL, Unidade GENOTOX—ROYAL, Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43421, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
| | - Daniel Prá
- Laboratório de Reparação de DNA em Eucariotos, Departamento de Biofísica/Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43422, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
- PPG em Promoção da Saúde, Universidade de Santa Cruz do Sul (UNISC), Avenida Independência 2293, 96815-900 Santa Cruz do Sul, RS, Brazil
| | - João Antonio Pêgas Henriques
- Laboratório de Reparação de DNA em Eucariotos, Departamento de Biofísica/Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43422, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
- Instituto de Educação para Pesquisa, Desenvolvimento e Inovação Tecnológica—ROYAL, Unidade GENOTOX—ROYAL, Centro de Biotecnologia, UFRGS, Avenida Bento Gonçalves 9500, Prédio 43421, Setor IV, Campus do Vale, 91501-970 Porto Alegre, RS, Brazil
- Instituto de Biotecnologia, Departamento de Ciências Biomédicas, Universidade de Caxias do Sul (UCS), Rua Francisco Getúlio Vargas 1130, 95070-560 Caxias do Sul, RS, Brazil
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26
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Haddad NF, Teodoro AJ, Leite de Oliveira F, Soares N, de Mattos RM, Hecht F, Dezonne RS, Vairo L, Goldenberg RCDS, Gomes FCA, de Carvalho DP, Gadelha MR, Nasciutti LE, Miranda-Alves L. Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells. PLoS One 2013; 8:e62773. [PMID: 23667519 PMCID: PMC3647049 DOI: 10.1371/journal.pone.0062773] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Accepted: 03/25/2013] [Indexed: 12/21/2022] Open
Abstract
Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1) in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27(kip1) in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1); and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.
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Affiliation(s)
- Natália F. Haddad
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
- Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil
| | - Anderson J. Teodoro
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
- Programa de Nutrição e Alimentos, Universidade do Estado do Rio de Janeiro, Brazil
| | | | - Nathália Soares
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
| | | | - Fábio Hecht
- Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil
| | | | - Leandro Vairo
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil
| | | | | | - Denise Pires de Carvalho
- Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil
| | - Mônica R. Gadelha
- Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil
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27
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Azqueta A, Collins AR. Carotenoids and DNA damage. Mutat Res 2012; 733:4-13. [PMID: 22465157 DOI: 10.1016/j.mrfmmm.2012.03.005] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2011] [Revised: 03/12/2012] [Accepted: 03/13/2012] [Indexed: 12/22/2022]
Abstract
Carotenoids are among the best known antioxidant phytochemicals, and are widely believed to contribute to the health-promoting properties of fruits and vegetables. Investigations of the effects of carotenoids have been carried out at different levels: in cultured cells, in experimental animals, and in humans. Studying reports from the last 5 years, we find a clear distinction between effects of vitamin A and pro-vitamin A carotenoids (the carotenes and β-cryptoxanthin), and effects of non-vitamin A carotenoids (lycopene, lutein, astaxanthin and zeaxanthin). Whereas the latter group are almost invariably reported to protect against DNA damage, whether endogenous or induced by exogenous agents, the provitamin A carotenoids show a more varied spectrum of effects, sometimes protecting and sometimes enhancing DNA damage. The tendency to exacerbate damage is seen mainly at high concentrations, and might be accounted for by pro-oxidant actions of these carotenoids.
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Affiliation(s)
- Amaya Azqueta
- Department of Nutrition, Food Science and Toxicology, Schools of Pharmacy and Sciences, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain
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