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Wang Z, Liu S, Zhang M, Liu M. Dual roles of methylglyoxal in cancer. Front Oncol 2025; 15:1557162. [PMID: 40352588 PMCID: PMC12061732 DOI: 10.3389/fonc.2025.1557162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 04/04/2025] [Indexed: 05/14/2025] Open
Abstract
Cancer treatment currently includes a variety of approaches. Chemotherapy, targeted therapy, and immunotherapy are combined based on cancer characteristics to develop personalized treatment plans. However, drug resistance can hinder the progress of treatment over time. Methylglyoxal (MG) is a metabolite with hormesis, exhibiting both pro-tumor and anti-tumor actions depending on its concentration during cancer progression. The MG-related metabolic pathway is being explored in the development of anti-cancer drugs, focusing on reducing MG stress or exploiting its cytotoxic effects to inhibit cancer progression. This article investigates the dual role of MG in cancer, emphasizing its effects on cell metabolism and tumor progression. It proposes MG capture therapy for the pre-cancerous stage and MG toxicity therapy for the cancer stage, contributing to the development of precise and individualized cancer treatments.
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Affiliation(s)
| | | | | | - Min Liu
- Department of Oncology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China
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Hansman DS, Du J, Casson RJ, Peet DJ. Eye on the horizon: The metabolic landscape of the RPE in aging and disease. Prog Retin Eye Res 2025; 104:101306. [PMID: 39433211 PMCID: PMC11833275 DOI: 10.1016/j.preteyeres.2024.101306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/10/2024] [Accepted: 10/10/2024] [Indexed: 10/23/2024]
Abstract
To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress - all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.
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Affiliation(s)
- David S Hansman
- School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
| | - Jianhai Du
- Department of Ophthalmology and Visual Sciences, Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, WV 26506, USA
| | - Robert J Casson
- Discipline of Ophthalmology and Visual Science, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
| | - Daniel J Peet
- School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia
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3
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Li J, Roshelli Baker J, Aglago EK, Zhao Z, Jiao L, Freisling H, Hughes DJ, Eriksen AK, Tjønneland A, Severi G, Katzke V, Kaaks R, Schulze MB, Masala G, Pala V, Pasanisi F, Tumino R, Padroni L, Vermeulen RCH, Gram IT, Braaten T, Jakszyn PG, Sánchez MJ, Gómez-Gómez JH, Moreno-Iribas C, Amiano P, Papier K, Weiderpass E, Huybrechts I, Heath AK, Schalkwijk C, Jenab M, Fedirko V. Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients. Int J Cancer 2024; 155:1982-1995. [PMID: 39057841 DOI: 10.1002/ijc.35114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/22/2024] [Accepted: 05/10/2024] [Indexed: 07/28/2024]
Abstract
Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.
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Affiliation(s)
- Jinze Li
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jacqueline Roshelli Baker
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Elom K Aglago
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - Zhiwei Zhao
- Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Li Jiao
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Heinz Freisling
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - David J Hughes
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Anne Kirstine Eriksen
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Anne Tjønneland
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Gianluca Severi
- Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France
- Department of Statistics, Computer Science, Applications "G. Parenti", University of Florence, Florence, Italy
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute for Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - Giovanna Masala
- Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy
| | - Valeria Pala
- Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy
| | - Fabrizio Pasanisi
- Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE ONLUS, Ragusa, Italy
| | - Lisa Padroni
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, and Center for Cancer Prevention (CPO), Turin, Italy
| | - Roel C H Vermeulen
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Inger T Gram
- Faculty of Health Sciences, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Tonje Braaten
- Faculty of Health Sciences, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Paula Gabriela Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
| | - Maria-José Sánchez
- Escuela Andaluza de Salud Pública (EASP), Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Jesús-Humberto Gómez-Gómez
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain
| | - Conchi Moreno-Iribas
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Pilar Amiano
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain
- BioGipuzkoa (BioDonostia) Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain
| | - Keren Papier
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Inge Huybrechts
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Casper Schalkwijk
- Laboratory of Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Center, The Netherlands
| | - Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - Veronika Fedirko
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
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Jing PF, Chen J, Yu ED, Miao CY. Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer. World J Gastrointest Oncol 2024; 16:2429-2438. [PMID: 38994158 PMCID: PMC11236233 DOI: 10.4251/wjgo.v16.i6.2429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 03/03/2024] [Accepted: 04/09/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND In recent years, the incidence of colorectal cancer (CRC) has been increasing. With the popularization of endoscopic technology, a number of early CRC has been diagnosed. However, despite current treatment methods, some patients with early CRC still experience postoperative recurrence and metastasis. AIM To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations. METHODS A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study. Results of blood routine test, liver and kidney function tests and tumor markers were collected before surgery. Patients were followed up through disease-specific database and telephone interviews. Tumor recurrence, metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis. RESULTS We comprehensively compared the predictive value of preoperative blood routine, blood biochemistry and tumor markers for disease-free survival (DFS) and overall survival (OS) of CRC. Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS [hazard ratio (HR) = 0.995, 95% confidence interval (CI): 0.991-0.999, P = 0.015], while serum carcinoembryonic antigen (CEA) level (HR = 1.008, 95%CI: 1.001-1.016, P = 0.027) and serum total cholesterol level (HR = 1.538, 95%CI: 1.026-2.305, P = 0.037) were independent risk factors for OS. The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL. Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level, the difference between the two groups was not statistically significant (P = 0.075). CONCLUSION For patients with T2N0M0 or T3N0M0 CRC, preoperative platelet count was a protective factor for DFS, while serum CEA level was an independent risk factor for OS. Given that these measures are easier to detect and more acceptable to patients, they may have broader applications.
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Affiliation(s)
- Peng-Fei Jing
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
| | - Jin Chen
- Department of Endocrinology and Metabolism, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
| | - En-Da Yu
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
| | - Chao-Yu Miao
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, China
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Jing PF, Chen J, Yu ED, Miao CY. Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer. World J Gastrointest Oncol 2024; 16:2417-2426. [DOI: 10.4251/wjgo.v16.i6.2417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 03/03/2024] [Accepted: 04/09/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND In recent years, the incidence of colorectal cancer (CRC) has been increasing. With the popularization of endoscopic technology, a number of early CRC has been diagnosed. However, despite current treatment methods, some patients with early CRC still experience postoperative recurrence and metastasis.
AIM To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations.
METHODS A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study. Results of blood routine test, liver and kidney function tests and tumor markers were collected before surgery. Patients were followed up through disease-specific database and telephone interviews. Tumor recurrence, metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis.
RESULTS We comprehensively compared the predictive value of preoperative blood routine, blood biochemistry and tumor markers for disease-free survival (DFS) and overall survival (OS) of CRC. Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS [hazard ratio (HR) = 0.995, 95% confidence interval (CI): 0.991-0.999, P = 0.015], while serum carcinoembryonic antigen (CEA) level (HR = 1.008, 95%CI: 1.001-1.016, P = 0.027) and serum total cholesterol level (HR = 1.538, 95%CI: 1.026-2.305, P = 0.037) were independent risk factors for OS. The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL. Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level, the difference between the two groups was not statistically significant (P = 0.075).
CONCLUSION For patients with T2N0M0 or T3N0M0 CRC, preoperative platelet count was a protective factor for DFS, while serum CEA level was an independent risk factor for OS. Given that these measures are easier to detect and more acceptable to patients, they may have broader applications.
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Affiliation(s)
- Peng-Fei Jing
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
| | - Jin Chen
- Department of Endocrinology and Metabolism, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
| | - En-Da Yu
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China
| | - Chao-Yu Miao
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, China
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Si C, Liu F, Peng Y, Qiao Y, Wang P, Wang X, Gong J, Zhou H, Zhang M, Song F. Association of total and different food-derived advanced glycation end-products with risks of all-cause and cause-specific mortality. Food Funct 2024; 15:1553-1561. [PMID: 38235609 DOI: 10.1039/d3fo03945e] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2024]
Abstract
Background: advanced glycation end-products (AGEs), formed through a series of non-enzymatic reactions, can promote inflammation and oxidative stress. Their accumulation in the body has been linked to cardiovascular disease (CVD) and cancer. However, the association of total AGEs and AGEs from different food sources with risks of all-cause, CVD, and cancer mortality is still unknown. Methods: we conducted a prospective cohort study of a nationally representative sample of 22 124 participants from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2003-2006. A food frequency questionnaire (FFQ) was utilized to calculate total and different food-derived AGE intake. Associations between various dietary AGE scores and the risk of all-cause, CVD, and cancer mortality were assessed by weighted Cox proportional hazard regression models. Results: over a median follow-up period of 27.1 years, we found that in the general population, AGE scores of both baked foods and meat were risk factors for all-cause, CVD, and cancer mortality. Specially, higher AGE scores in total and those derived from 10 of the 13 food groups were statistically associated with an increased risk of CVD mortality. Egg-, fruit-, and vegetable-derived AGE scores were positively correlated with the risk of cancer mortality. Additionally, there were positive multiplicative and additive interactions between smoking and meat-derived AGE scores on all-cause mortality. Conclusions: high amounts of AGE consumption is associated with an increased risk of CVD mortality, and meat and baked food-derived AGEs were positively linked to all-cause, CVD, and cancer mortalities. Adherence to unhealthy lifestyles, such as smoking, may increase mortality from leading causes in individuals with AGE-enriched diet habits.
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Affiliation(s)
- Changyu Si
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Fubin Liu
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Yu Peng
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Yating Qiao
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Peng Wang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Xixuan Wang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Jianxiao Gong
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Huijun Zhou
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
| | - Ming Zhang
- Comprehensive Management Department of Occupational Health, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, 518020, China.
| | - Fangfang Song
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
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Bangar NS, Gvalani A, Ahmad S, Khan MS, Tupe RS. Understanding the role of glycation in the pathology of various non-communicable diseases along with novel therapeutic strategies. Glycobiology 2022; 32:1068-1088. [PMID: 36074518 DOI: 10.1093/glycob/cwac060] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 08/10/2022] [Accepted: 09/02/2022] [Indexed: 01/07/2023] Open
Abstract
Glycation refers to carbonyl group condensation of the reducing sugar with the free amino group of protein, which forms Amadori products and advanced glycation end products (AGEs). These AGEs alter protein structure and function by configuring a negative charge on the positively charged arginine and lysine residues. Glycation plays a vital role in the pathogenesis of metabolic diseases, brain disorders, aging, and gut microbiome dysregulation with the aid of 3 mechanisms: (i) formation of highly reactive metabolic pathway-derived intermediates, which directly affect protein function in cells, (ii) the interaction of AGEs with its associated receptors to create oxidative stress causing the activation of transcription factor NF-κB, and (iii) production of extracellular AGEs hinders interactions between cellular and matrix molecules affecting vascular and neural genesis. Therapeutic strategies are thus required to inhibit glycation at different steps, such as blocking amino and carbonyl groups, Amadori products, AGEs-RAGE interactions, chelating transition metals, scavenging free radicals, and breaking crosslinks formed by AGEs. The present review focused on explicitly elaborating the impact of glycation-influenced molecular mechanisms in developing and treating noncommunicable diseases.
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Affiliation(s)
- Nilima S Bangar
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India
| | - Armaan Gvalani
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India
| | - Saheem Ahmad
- Department of Medical Laboratory Sciences, University of Hail, Hail City 2440, Saudi Arabia
| | - Mohd S Khan
- Department of Biochemistry, Protein Research Chair, King Saud University, Riyadh 11451, Saudi Arabia
| | - Rashmi S Tupe
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India
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Berisha A, Shutkind K, Borniger JC. Sleep Disruption and Cancer: Chicken or the Egg? Front Neurosci 2022; 16:856235. [PMID: 35663547 PMCID: PMC9160986 DOI: 10.3389/fnins.2022.856235] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Sleep is a nearly ubiquitous phenomenon across the phylogenetic tree, highlighting its essential role in ensuring fitness across evolutionary time. Consequently, chronic disruption of the duration, timing, or structure of sleep can cause widespread problems in multiple physiological systems, including those that regulate energy balance, immune function, and cognitive capacity, among others. Many, if not all these systems, become altered throughout the course of cancer initiation, growth, metastatic spread, treatment, and recurrence. Recent work has demonstrated how changes in sleep influence the development of chronic diseases, including cancer, in both humans and animal models. A common finding is that for some cancers (e.g., breast), chronic disruption of sleep/wake states prior to disease onset is associated with an increased risk for cancer development. Additionally, sleep disruption after cancer initiation is often associated with worse outcomes. Recently, evidence suggesting that cancer itself can affect neuronal circuits controlling sleep and wakefulness has accumulated. Patients with cancer often report difficulty falling asleep, difficulty staying asleep, and severe fatigue, during and even years after treatment. In addition to the psychological stress associated with cancer, cancer itself may alter sleep homeostasis through changes to host physiology and via currently undefined mechanisms. Moreover, cancer treatments (e.g., chemotherapy, radiation, hormonal, and surgical) may further worsen sleep problems through complex biological processes yet to be fully understood. This results in a "chicken or the egg" phenomenon, where it is unclear whether sleep disruption promotes cancer or cancer reciprocally disrupts sleep. This review will discuss existing evidence for both hypotheses and present a framework through which the interactions between sleep and cancer can be dissociated and causally investigated.
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Affiliation(s)
- Adrian Berisha
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States
| | - Kyle Shutkind
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States
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Dawood M, Younus ZM, Alnori M, Mahmood S. The Biological Role of Advanced Glycation End Products in the Development and Progression of Colorectal Cancer. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
“Colorectal cancer” (CRC) is one of the most prevalent cancers, posing a scientific challenge and serving as a model for investigating the molecular pathways underlying its development. “Advanced glycation end products” (AGEs) have drawn interest in this context. The buildup of these diverse, chemically complex groups, which are formed by a “non-enzymatic interaction” between reducing sugar and a range of macromolecules, significantly increases “inflammation and oxidative stress” in the body, which has long been associated to cancer formation. The traditional pathways that promote AGE formation, as well as the significance of AGEs’ interaction with the receptor for “advanced glycation end products” (RAGE) and other means involved in CRC initiation and progression, are discussed in this review.
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10
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Mollace A, Coluccio ML, Donato G, Mollace V, Malara N. Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy. Oncotarget 2021; 12:1281-1295. [PMID: 34194625 PMCID: PMC8238251 DOI: 10.18632/oncotarget.27990] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/02/2021] [Indexed: 12/19/2022] Open
Abstract
The tumour microenvironment is the result of the activity of many types of cells in various metabolic states, whose metabolites are shared between cells. This cellular complexity results in an availability profile of nutrients and reactive metabolites such as advanced glycation end products (AGE). The tumour microenvironment is not favourable to immune cells due to hypoxia and for the existence of significant competition between various types of cells for a limited nutrient pool. However, it is now known that cancer cells can influence the host's immune reaction through the expression and secretion of numerous molecules. The microenvironment can therefore present itself in different patterns that contribute to shaping immune surveillance. Colorectal cancer (CRC) is one of the most important causes of death in cancer patients. Recently, immunotherapy has begun to give encouraging results in some groups of patients suffering from this neoplasm. The analysis of literature data shows that the RAGE (Receptor for advanced glycation end products) and its numerous ligands contribute to connect the energy metabolic pathway, which appears prevalently disconnected by mitochondrial running, with the immune reaction, conditioned by local microbiota and influencing tumour growth. Understanding how metabolism in cancer and immune cells shapes response and resistance to therapy, will provide novel potential strategies to increase both the number of tumour types treated by immunotherapy and the rate of immunotherapy response. The analysis of literature data shows that an immunotherapy approach based on the knowledge of RAGE and its ligands is not only possible, but also desirable in the treatment of CRC.
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Affiliation(s)
- Annachiara Mollace
- Department of Health Sciences, Research Centre IRC-FSH, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Maria Laura Coluccio
- Department of Experimental and Clinical Medicine, Bionem Laboratory, Magna Græcia University of Catanzaro, 88100 Catanzaro, Italy
| | - Giuseppe Donato
- Department of Health Sciences, University Magna Græcia of Catanzaro, Campus S. Venuta, 88100 Catanzaro, Italy
| | - Vincenzo Mollace
- Department of Health Sciences, Research Centre IRC-FSH, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy.,These authors contributed equally to this work
| | - Natalia Malara
- Department of Experimental and Clinical Medicine, Bionem Laboratory, Magna Græcia University of Catanzaro, 88100 Catanzaro, Italy.,These authors contributed equally to this work
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11
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Sahingoz Erdal G, Yaman M, Servi EY, Ugur H, Kasapoglu P, Cikot M, Isiksacan N. Measurement of Advanced Glycation End Products Could Be Used as an Indicator of Unhealthy Nutrition for Colorectal Cancer Risk. Nutr Cancer 2021; 74:896-902. [PMID: 34142632 DOI: 10.1080/01635581.2021.1938148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The main culprit behind most cancers is the accumulation of reactive oxygen species. Glyoxal (GO) and methylglyoxal (MGO) are reactive intermediates created by food processing and they are precursors of advanced glycation end products (AGE) that cause glycative stress. We aimed to evaluate the relationship between AGE levels of healthy volunteers and treatment-naive patients diagnosed with colorectal cancer. The study consisted of patients diagnosed with colorectal cancer and healthy volunteers who underwent routine colonoscopy. The study was conducted with a total of 42 cases, 47.6% (n = 20) female. The ages of the participants in the study ranged from 41 to 82 years, and the mean was 60.57 ± 10.78 years. The GO and MGO values of the patient group were found to be significantly higher than those of the control group (p = 0.007, p = 0.001, respectively). The risk of colorectal cancer was 22 and 57 times higher in individuals with GO and MGO values above 1.25 μg/mL and 0.0095 μg/mL, respectively. The blood AGE level is closely related to diet, and it can be decreased through the appropriate improvement of diet. Thus, the measurement of AGE can be used to predict whether a person's nutrition is healthy or unhealthy and prevent increased risk of colorectal cancer.
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Affiliation(s)
- Gulcin Sahingoz Erdal
- Department of Oncology, University of Health Sciences, Istanbul, Turkey.,Department of Immunology, University of Health Sciences, Istanbul, Turkey
| | - Mustafa Yaman
- Department of Nutrition and Dietetics, Sabahattin Zaim University, Istanbul, Turkey
| | - Esra Yıldırım Servi
- Department of Nutrition and Dietetics, Sabahattin Zaim University, Istanbul, Turkey
| | - Halime Ugur
- Department of Nutrition and Dietetics, Medipol University Istanbul, Istanbul, Turkey
| | - Pinar Kasapoglu
- Department of Biochemistry, University of Health Sciences, Istanbul, Turkey
| | - Murat Cikot
- Department of General Surgery, University of Health Sciences, Istanbul, Turkey
| | - Nilgun Isiksacan
- Department of Immunology, University of Health Sciences, Istanbul, Turkey.,Department of Biochemistry, University of Health Sciences, Istanbul, Turkey
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12
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Aglago EK, Schalkwijk CG, Freisling H, Fedirko V, Hughes DJ, Jiao L, Dahm CC, Olsen A, Tjønneland A, Katzke V, Johnson T, Schulze MB, Aleksandrova K, Masala G, Sieri S, Simeon V, Tumino R, Macciotta A, Bueno-de-Mesquita B, Skeie G, Gram IT, Sandanger T, Jakszyn P, Sánchez MJ, Amiano P, Colorado-Yohar SM, Gurrea AB, Perez-Cornago A, Mayén AL, Weiderpass E, Gunter MJ, Heath AK, Jenab M. Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study. Carcinogenesis 2021; 42:705-713. [PMID: 33780524 PMCID: PMC8162627 DOI: 10.1093/carcin/bgab026] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 03/02/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs-Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)-were measured by ultra-performance liquid chromatography-tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27-0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53-1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37-0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.
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Affiliation(s)
- Elom K Aglago
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
| | - Casper G Schalkwijk
- Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Heinz Freisling
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
| | - Veronika Fedirko
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - David J Hughes
- Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland
| | - Li Jiao
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | | | - Anja Olsen
- Department of Public Health, Aarhus University, Aarhus, Denmark
- Danish Cancer Society Research Center, København, Denmark
| | - Anne Tjønneland
- Danish Cancer Society Research Center, København, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Theron Johnson
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany
| | - Krasimira Aleksandrova
- Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
| | - Giovanna Masala
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy
| | - Vittorio Simeon
- Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, University ‘Luigi Vanvitelli’, Napoli, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy
| | - Alessandra Macciotta
- Department of Clinical and Biological Sciences, University of Turin, Torino, Italy
| | - Bas Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands
| | - Guri Skeie
- Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Inger Torhild Gram
- Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Torkjel Sandanger
- Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Paula Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain
- Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain
| | - Maria-Jose Sánchez
- Escuela Andaluza de Salud Pública (EASP), Granada, Spain
- Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain
- Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Pilar Amiano
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain
| | - Sandra M Colorado-Yohar
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia
| | - Aurelio Barricarte Gurrea
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Navarra Public Health Institute, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Aurora Perez-Cornago
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Ana-Lucia Mayén
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
| | - Elisabete Weiderpass
- Office of the Director, International Agency for Research on Cancer (IARC), Lyon, France
| | - Marc J Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Mazda Jenab
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
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13
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Senavirathna L, Ma C, Chen R, Pan S. Proteomic Investigation of Glyceraldehyde-Derived Intracellular AGEs and Their Potential Influence on Pancreatic Ductal Cells. Cells 2021; 10:cells10051005. [PMID: 33923186 PMCID: PMC8145644 DOI: 10.3390/cells10051005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/14/2021] [Accepted: 04/23/2021] [Indexed: 02/07/2023] Open
Abstract
Glyceraldehyde-derived advanced glycation end products (AGEs) play an important role in the pathogenesis of many diseases including cancer. Accumulation of intracellular AGEs could stimulate cancer induction and facilitate cancer progression. We evaluated the toxic effect of glyceraldehyde-derived intracellular AGEs on normal and malignant pancreatic ductal cells by assessing the cell viability, toxicity, and oxidative stress, followed by proteomic analysis. Our functional studies showed that pancreatic cancer cells (PANC-1 and MIA PaCa-2) were more resistant to glyceraldehyde treatment compared to normal pancreatic ductal epithelial cells (HPDE), while cytotoxicity effects were observed in all cell types. Furthermore, using 13C isotopic labeled glyceraldehyde, the proteomic data revealed a dose-dependent increment of the number of glycation adducts in both these cell types. HPDE cells showed a higher number of intracellular AGEs compared to cancer cells. At a molecular level, the glycations in the lysine residues of proteins showed a concurrent increase with the concentration of the glyceraldehyde treatment, while the arginine glycations appeared to be less affected by the glyceraldehyde doses. Further pathway analysis of these glycated proteins suggested that the glycated proteins participate in important biological processes that are major hallmarks of cancer initiation and progression, including metabolic processes, immune response, oxidative stress, apoptosis, and S100 protein binding.
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Affiliation(s)
- Lakmini Senavirathna
- The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.S.); (C.M.)
| | - Cheng Ma
- The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.S.); (C.M.)
| | - Ru Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Sheng Pan
- The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.S.); (C.M.)
- Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Correspondence:
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14
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Beeraka NM, Bovilla VR, Doreswamy SH, Puttalingaiah S, Srinivasan A, Madhunapantula SV. The Taming of Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) Deglycation by Fructosamine-3-Kinase (FN3K)-Inhibitors-A Novel Strategy to Combat Cancers. Cancers (Basel) 2021; 13:cancers13020281. [PMID: 33466626 PMCID: PMC7828646 DOI: 10.3390/cancers13020281] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Aim of this review is to provide an overview on (a) Fructosamine-3-Kinase (FN3K) and its role in regulating Nuclear Factor Erythorid-2-Related Factor-2 (Nrf2); (b) the role of glycation and deglycation mechanisms in modulating the functional properties of proteins, in particular, the Nrf2; (c) the dual role of Nrf2 in the prevention and treatment of cancers. Since controlling the glycation of Nrf2 is one of the key mechanisms determining the fate of a cell; whether to get transformed into a cancerous one or to stay as a normal one, it is important to regulate Nrf2 and deglycating FN3K using pharmacological agents. Inhibitors of FN3K are being explored currently to modulate Nrf2 activity thereby control the cancers. Abstract Glycated stress is mediated by the advanced glycation end products (AGE) and the binding of AGEs to the receptors for advanced glycation end products (RAGEs) in cancer cells. RAGEs are involved in mediating tumorigenesis of multiple cancers through the modulation of several downstream signaling cascades. Glycated stress modulates various signaling pathways that include p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa–B (NF-κB), tumor necrosis factor (TNF)-α, etc., which further foster the uncontrolled proliferation, growth, metastasis, angiogenesis, drug resistance, and evasion of apoptosis in several cancers. In this review, a balanced overview on the role of glycation and deglycation in modulating several signaling cascades that are involved in the progression of cancers was discussed. Further, we have highlighted the functional role of deglycating enzyme fructosamine-3-kinase (FN3K) on Nrf2-driven cancers. The activity of FN3K is attributed to its ability to deglycate Nrf2, a master regulator of oxidative stress in cells. FN3K is a unique protein that mediates deglycation by phosphorylating basic amino acids lysine and arginine in various proteins such as Nrf2. Deglycated Nrf2 is stable and binds to small musculoaponeurotic fibrosarcoma (sMAF) proteins, thereby activating cellular antioxidant mechanisms to protect cells from oxidative stress. This cellular protection offered by Nrf2 activation, in one way, prevents the transformation of a normal cell into a cancer cell; however, in the other way, it helps a cancer cell not only to survive under hypoxic conditions but also, to stay protected from various chemo- and radio-therapeutic treatments. Therefore, the activation of Nrf2 is similar to a double-edged sword and, if not controlled properly, can lead to the development of many solid tumors. Hence, there is a need to develop novel small molecule modulators/phytochemicals that can regulate FN3K activity, thereby maintaining Nrf2 in a controlled activation state.
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Affiliation(s)
- Narasimha M. Beeraka
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India; (N.M.B.); (V.R.B.); (S.H.D.); (S.P.)
| | - Venugopal R. Bovilla
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India; (N.M.B.); (V.R.B.); (S.H.D.); (S.P.)
- Public Health Research Institute of India (PHRII), Mysuru, Karnataka 570020, India
| | - Shalini H. Doreswamy
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India; (N.M.B.); (V.R.B.); (S.H.D.); (S.P.)
| | - Sujatha Puttalingaiah
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India; (N.M.B.); (V.R.B.); (S.H.D.); (S.P.)
| | - Asha Srinivasan
- Division of Nanoscience and Technology, Faculty of Life Sciences, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India;
| | - SubbaRao V. Madhunapantula
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India; (N.M.B.); (V.R.B.); (S.H.D.); (S.P.)
- Special Interest Group in Cancer Biology and Cancer Stem Cells, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India
- Correspondence: ; Tel.: +91-810-527-8621
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15
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Zhou X, Lin N, Zhang M, Wang X, An Y, Su Q, Du P, Li B, Chen H. Circulating soluble receptor for advanced glycation end products and other factors in type 2 diabetes patients with colorectal cancer. BMC Endocr Disord 2020; 20:170. [PMID: 33187505 PMCID: PMC7666469 DOI: 10.1186/s12902-020-00647-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 10/31/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. METHODS A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. RESULTS Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037-5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P < 0.001), total cholesterol (r = 0.491, P < 0.001), and low-density lipoprotein cholesterol (LDL-c)(r = 0.330, P < 0.001) levels; the homeostatic model assessment for insulin resistance(HOMA-IR)score (r = 0.194, P = 0.017); and fasting serum insulin (r = 0.167, P = 0.041) and IL-6 (r = 0.311, P < 0.001) concentrations. CONCLUSIONS Our results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.
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Affiliation(s)
- Xiaohai Zhou
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China
| | - Ning Lin
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China
| | - Mingjie Zhang
- Shanghai Jiahui International Hospital, 689 Guiping Road, Xuhui District, Shanghai, China
| | - Xiaoling Wang
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China
| | - Ye An
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China
| | - Peng Du
- Department of Colorectal Surgery, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China.
| | - Bo Li
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China.
| | - Hanbei Chen
- Department of Endocrinology, Xinhua Hospital affiliated with Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, China.
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16
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Nagata C, Wada K, Yamakawa M, Nakashima Y, Koda S, Uji T, Oba S. Dietary Intake of Nε-carboxymethyl-lysine, a Major Advanced Glycation End Product, is Not Associated with Increased Risk of Mortality in Japanese Adults in the Takayama Study. J Nutr 2020; 150:2799-2805. [PMID: 32840609 DOI: 10.1093/jn/nxaa230] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 01/30/2020] [Accepted: 07/09/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Although endogenous advanced glycation end products (AGEs) have been implicated in the development of various chronic diseases, whether AGEs in foods represent a risk to human health remains unknown. OBJECTIVES We aimed to estimate the intake of Nε-carboxymethyl-lysine (CML), a major AGE product, using a database of CML contents on LC-MS methods, and to examine CML's association with total and cause-specific mortality in Japanese adults. METHODS The analysis included 13,355 men and 15,724 women, aged 35 years and older, from the Takayama study. They responded to a self-administered questionnaire in 1992. Their diet, including the CML intake, was assessed using a food-frequency questionnaire at baseline. Mortality was ascertained during 16 years of follow-up. HRs and 95% CIs for mortality were estimated separately for men and women according to CMI quartiles. RESULTS We noted 2901 deaths in men and 2438 deaths in women during the follow-up. In men, as compared with the lowest quartile of intake, the highest quartile of CML was inversely associated with the risks of both total and non-cancer, non-cardiovascular disease mortality after controlling for covariates [HR = 0.89 (95% CI, 0.79-1.00; P-trend = 0.047) and HR = 0.74 (95% CI, 0.58-0.94; P-trend = 0.03), respectively]. However, stratified analyses showed both inverse and positive associations between CML intake and cause-specific mortality in women, depending on their characteristics. For example, years of education had a modifying effect on both the CML intake and non-cancer, non-cardiovascular disease mortality in women. In men, the associations of CML intake with mortality depended on food sources. CONCLUSIONS Overall, the present study does not support a positive association between CML intake and mortality in Japanese adults. The potential relevance of the food source of CML to the link between dietary CML and mortality warrants further attention.
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Affiliation(s)
- Chisato Nagata
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Keiko Wada
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Michiyo Yamakawa
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuma Nakashima
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Sachi Koda
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takahiro Uji
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Shno Oba
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.,Graduate School of Health Sciences, Gunma University, Gunma, Japan
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17
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Wan J, Wu X, Chen H, Xia X, Song X, Chen S, Lu X, Jin J, Su Q, Cai D, Liu B, Li B. Aging-induced aberrant RAGE/PPARα axis promotes hepatic steatosis via dysfunctional mitochondrial β oxidation. Aging Cell 2020; 19:e13238. [PMID: 32936538 PMCID: PMC7576254 DOI: 10.1111/acel.13238] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 07/18/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Non‐alcoholic fatty liver disease (NAFLD), characterized by an increase in hepatic triglyceride (TG) content, is the most common liver disease worldwide. Aging has been shown to increase susceptibility to NAFLD; however, the underlying molecular mechanism remains poorly understood. In the present study, we examined hepatic TG content and gene expression profiles in body weight‐matched young (3 months old), middle‐aged (10 months old), and old (20 months old) C57BL/6 mice and found that TGs were markedly accumulated while mitochondrial β‐oxidation‐related genes, including PPARα, were downregulated in the liver of old mice. In addition, advanced glycation end product receptor (RAGE), a key regulator of glucose metabolism, was upregulated in the old mice. Mechanistically, suppression of RAGE upregulated PPARα and its downstream target genes, which in turn led to reduced TG retention. Finally, we found that hepatic RAGE expression was increased in aging patients, a finding that correlated with decreased PPARα levels. Taken together, our findings demonstrate that the upregulation of RAGE may play a critical role in aging‐associated liver steatosis.
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Affiliation(s)
- Jian Wan
- Department of Emergency and Critical Care Medicine Shanghai Pudong New Area People's Hospital Shanghai University of Medicine and Health Sciences Shanghai China
| | - Xiangsong Wu
- Department of General Surgery XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Hanbei Chen
- Department of Endocrinology XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Xinyi Xia
- Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China
| | - Xi Song
- Department of Emergency and Critical Care Medicine Shanghai Pudong New Area People's Hospital Shanghai University of Medicine and Health Sciences Shanghai China
| | - Song Chen
- Department of Emergency and Critical Care Medicine Shanghai Pudong New Area People's Hospital Shanghai University of Medicine and Health Sciences Shanghai China
| | - Xinyuan Lu
- Department of Emergency and Critical Care Medicine Shanghai Pudong New Area People's Hospital Shanghai University of Medicine and Health Sciences Shanghai China
| | - Jie Jin
- Department of Endocrinology XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Qing Su
- Department of Endocrinology XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Dongsheng Cai
- Department of Molecular Pharmacology Diabetes Research Center Institute of Aging Albert Einstein College of Medicine Bronx NY USA
| | - Bin Liu
- Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention Hubei Polytechnic University School of Medicine Huangshi China
| | - Bo Li
- Department of Endocrinology XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
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18
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Dariya B, Nagaraju GP. Advanced glycation end products in diabetes, cancer and phytochemical therapy. Drug Discov Today 2020; 25:1614-1623. [PMID: 32652310 DOI: 10.1016/j.drudis.2020.07.003] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/04/2020] [Accepted: 07/03/2020] [Indexed: 02/08/2023]
Abstract
The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimately leading to diabetes and cancers. In this review, we focus on the interaction of AGE-RAGE and their associated pathways. We also consider the activity of phytochemicals, such as genistein and curcumin, that trap dicarbonyl compounds including methylglyoxal (MG) and glyoxalase that arise from multiple pathways to block AGE formation and prevent its interaction with RAGE.
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Affiliation(s)
- Begum Dariya
- Department of Biosciences and Biotechnology, Banasthali University, Banasthali, Rajasthan 304022, India
| | - Ganji Purnachandra Nagaraju
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
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19
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El-Far AH, Sroga G, Al Jaouni SK, Mousa SA. Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression. Int J Mol Sci 2020; 21:ijms21103613. [PMID: 32443845 PMCID: PMC7279268 DOI: 10.3390/ijms21103613] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 05/02/2020] [Accepted: 05/08/2020] [Indexed: 12/26/2022] Open
Abstract
Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.
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Affiliation(s)
- Ali H. El-Far
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Damanhour 22511, Egypt;
| | - Grazyna Sroga
- Rensselaer Polytechnic Institute, NY (RPI), Troy, NY 12180, USA;
| | - Soad K. Al Jaouni
- Department of Hematology/Pediatric Oncology, King Abdulaziz University, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Shaker A. Mousa
- The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
- Correspondence:
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20
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Liang H. Advanced glycation end products induce proliferation, invasion and epithelial-mesenchymal transition of human SW480 colon cancer cells through the PI3K/AKT signaling pathway. Oncol Lett 2020; 19:3215-3222. [PMID: 32218866 PMCID: PMC7068709 DOI: 10.3892/ol.2020.11413] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 01/14/2020] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to determine the mechanism by which advanced glycation end products (AGEs) induce proliferation, invasion and epithelial-mesenchymal transition (EMT) of human colon cancer SW480 cells. SW480 cells were divided into groups as follows: i) Control; ii) cells treated with AGEs alone; and iii) cells treated with AGEs combined with LY294002. Proliferation, cell cycle progression, apoptosis, invasion and migration of SW480 cells were assessed using an MTT assay, flow cytometry, Transwell assays and a wound healing assay, respectively. The protein expression levels of PI3K, AKT and epithelial cadherin (E-cadherin) were examined by western blot analysis in SW480 cells treated with various concentrations of AGEs. Proliferation, invasion and migration were enhanced, cell cycle progression was increased and apoptosis was decreased in SW480 cells treated with AGEs compared with the control. The PI3K inhibitor, LY294002, reversed the effects of AGEs. Western blot analysis data demonstrated that AGEs increased the protein expression levels of PI3K and AKT, and decreased the expression of E-cadherin. The results suggested that AGEs exert a positive effect on the proliferation, invasion and EMT in SW480 cells through the PI3K/AKT signaling pathway.
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Affiliation(s)
- Huasheng Liang
- Institute of Endocrine and Metabolic Diseases, Beihai People's Hospital, Beihai, Guangxi Zhuang Autonomous Region 536000, P.R. China
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21
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Khan MS, Tabrez S, Al-Okail MS, Shaik GM, Bhat SA, Rehman TM, Husain FM, AlAjmi MF. Non-enzymatic glycation of protein induces cancer cell proliferation and its inhibition by quercetin: Spectroscopic, cytotoxicity and molecular docking studies. J Biomol Struct Dyn 2020; 39:777-786. [PMID: 31960772 DOI: 10.1080/07391102.2020.1715838] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Methylglyoxal (MG) is a potent glycating agent which reacts with proteins to form advanced glycation end products (AGEs). These chemically stable AGEs crosslink with proteins and could lead to amyloid formation that has the role in several diseases including Alzheimer's and Parkinson's. In this piece of work, glycation-induced conformational changes in HSA were observed with quenching of tryptophan fluorescence by 73.8% (41 nm red shift) and loss of hydrophobicity of HSA. CD spectroscopy result reaffirmed secondary structure changes in HSA. Moreover, MG-induced changes in HSA, proceeds to amyloid structure as characterized by an increase in thioflavin (ThT) fluorescence and transmission electron microscopy (TEM) images of HSA aggregates. Quercetin was found to inhibit both AGEs production and amyloid formation. Viability of MCF-7 cells was found to be increased with AGEs treatment, illustrating proliferation of cancer cells. Wound healing assay also revealed increased proliferation and migration of cells in the presence of AGEs. Additionally, molecular docking analyses were performed to demonstrate interactions involved in the stabilization of HSA-quercetin complex. The binding affinities of quercetin were found to be (K d = 105 M -1) much higher compared with MG (K d = 102 M -1). From this study, it is quite clear that quercetin reverses the effect of MG by sterically inhibiting the interaction between HSA and MG. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Mohd Shahnawaz Khan
- Protein Research Chair, Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Shams Tabrez
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Majed S Al-Okail
- Protein Research Chair, Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Gouse M Shaik
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Sheraz Ahmad Bhat
- Department of Biochemistry, SP College of Sciences, Cluster University of Srinagar, Jammu And Kashmir, India
| | - Tabish M Rehman
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Fohad Mabood Husain
- Department of Agriculture, Collage of Agriculture, Riyadh, King Saud University, Saudi Arabia
| | - Mohamed F AlAjmi
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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22
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Wang B, Yu J, Wang T, Shen Y, Lin D, Xu X, Wang Y. Identification of megakaryocytes as a target of advanced glycation end products in diabetic complications in bone marrow. Acta Diabetol 2018; 55:419-427. [PMID: 29417230 DOI: 10.1007/s00592-018-1109-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 01/17/2018] [Indexed: 10/18/2022]
Abstract
AIMS To define the possible effect of diabetic conditions on megakaryocytes, the long-know precursors of platelets and lately characterized modulator of hematopoietic stem quiescence-activation transition. METHODS Megakaryoblastic MEG-01 cell culture and TPO/SCF/IL-3-induced differentiation of human umbilical blood mononuclear cells toward megakaryocytes were used to test effects of glycated bovine serum albumin (BSA-AGEs). The ob/ob mice and streptozotocin-treated mice were used as models of hyperglycemia. MTT was used to measure cell proliferation, FACS for surface marker and cell cycle, and RT-qPCR for the expression of interested genes. Megakaryocytes at different stages in marrow smear were checked under microscope. RESULTS When added in MEG-01 cultures at 200 μg/ml, BSA-AGEs increased proliferation of cells and enhanced mRNA expression of RAGE, VEGFα and PF4 in the cells. None of cell cycle distribution, PMA-induced platelet-like particles production, expression of GATA1/NF-E2/PU-1/IL-6/OPG/PDGF in MEG-01 cells nor TPO/SCF/IL-3 induced umbilical cord blood cells differentiation into megakaryocyte was affected by BSA-AGEs. In the ob/ob diabetic mice, MKs percentages in marrow cells and platelets in peripheral blood were significantly increased compared with control mice. In streptozotocin-induced diabetic mice, however, MKs percentage in marrow cells was decreased though peripheral platelet counts were not altered. Gene expression assay showed that the change in MKs in these two diabetic conditions might be explained by the alteration of GATA1 and NF-E2 expression, respectively. CONCLUSIONS Diabetic condition in animals might exert its influence on hematopoiesis via megakaryocytes-the newly identified modulator of hematopoietic stem cells in bone marrow.
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Affiliation(s)
- Benfang Wang
- MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 708 Renmin Road, Suzhou, 215007, China
| | - Jianjiang Yu
- Department of Clinical Laboratory, The Affiliated Jiangyin Hospital of Southeast University, Jiangyin, 214400, China
| | - Ting Wang
- MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 708 Renmin Road, Suzhou, 215007, China
| | - Ying Shen
- MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 708 Renmin Road, Suzhou, 215007, China
| | - Dandan Lin
- MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 708 Renmin Road, Suzhou, 215007, China
| | - Xin Xu
- Department of Hematology, The Affiliated Jiangyin Hospital of Southeast University, Jiangyin, 214400, China
| | - Yiqiang Wang
- MOH Key Lab of Thrombosis and Hemostasis, Collaborative Innovation Center of Hematology-Thrombosis and Hemostasis Group, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, 708 Renmin Road, Suzhou, 215007, China.
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23
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Ahmad S, Khan H, Siddiqui Z, Khan MY, Rehman S, Shahab U, Godovikova T, Silnikov V, Moinuddin. AGEs, RAGEs and s-RAGE; friend or foe for cancer. Semin Cancer Biol 2018; 49:44-55. [DOI: 10.1016/j.semcancer.2017.07.001] [Citation(s) in RCA: 139] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 06/22/2017] [Accepted: 07/05/2017] [Indexed: 12/22/2022]
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24
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Ran H, Zhu Y, Deng R, Zhang Q, Liu X, Feng M, Zhong J, Lin S, Tong X, Su Q. Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN. J Exp Clin Cancer Res 2018; 37:54. [PMID: 29530061 PMCID: PMC5848567 DOI: 10.1186/s13046-018-0711-9] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 02/14/2018] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Diabetic patients have a higher risk factor for colorectal cancer (CRC) metastasis. Stearoyl-CoA desaturase 1 (SCD1), the main enzyme responsible for producing monounsaturated fatty acids(MUFA) from saturated fatty acids, is frequently deregulated in both diabetes and CRC. The function and mechanism of SCD1 in metastasis of CRC and its relevance to glucose remains largely unknown. METHODS SCD1 expression levels were analyzed in human CRC tissues and the Cancer Browser database ( https://genome-cancer.ucsc.edu/ ). CRC cell lines stably transfected with SCD1 shRNAs or vector were established to investigate the role of SCD1 in modulating migration and invasion of CRC cells. A glucose concentration gradient was set to investigate regulation of SCD1 in CRC relevant to diabetic conditions. RESULTS The clinical data analysis showed high expression of SCD1 in CRC tissues with a negative correlation with the prognosis of CRC. In vitro experiments revealed that SCD1 increased CRC progression through promoting epithelial-mesenchymal transition (EMT). Lipidomic analysis demonstrated that SCD1 increased MUFA levels and MUFA administration could rescue migration and invasion defect of CRC cells induced by SCD1 knockdown. Furthermore, SCD1-mediated progression of CRC was promoted by carbohydrate response-element binding protein (ChREBP) in response to high glucose. Mechanistically, hyperglycemia-SCD1-MUFA induced CRC cell migration and invasion by regulating PTEN. CONCLUSIONS Our findings show that SCD1 promotes metastasis of CRC cells through MUFA production and suppressing PTEN in response to glucose, which may be a novel mechanism for diabetes-induced CRC metastasis.
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Affiliation(s)
- Hui Ran
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092 China
| | - Yemin Zhu
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025 China
| | - Ruyuan Deng
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092 China
| | - Qi Zhang
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092 China
| | - Xisheng Liu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100, Haining Road, Shanghai, 200080 China
| | - Ming Feng
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025 China
| | - Jie Zhong
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025 China
| | - Shuhai Lin
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025 China
| | - Xuemei Tong
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025 China
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092 China
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25
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Lee KJ, Yoo JW, Kim YK, Choi JH, Ha TY, Gil M. Advanced glycation end products promote triple negative breast cancer cells via ERK and NF-κB pathway. Biochem Biophys Res Commun 2018; 495:2195-2201. [DOI: 10.1016/j.bbrc.2017.11.182] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 11/28/2017] [Indexed: 02/06/2023]
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26
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Ahmad S, Akhter F, Shahab U, Rafi Z, Khan MS, Nabi R, Khan MS, Ahmad K, Ashraf JM. Do all roads lead to the Rome? The glycation perspective! Semin Cancer Biol 2017; 49:9-19. [PMID: 29113952 DOI: 10.1016/j.semcancer.2017.10.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 10/29/2017] [Accepted: 10/30/2017] [Indexed: 12/11/2022]
Abstract
Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), β-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules. These alterations of gene expression can induce a normal cell to become a tumor cell. Glycative stress resulting from advanced glycation end products (AGEs) and reactive dicarbonyls can significantly affect cancer progression. AGEs are fashioned from the multifaceted chemical reaction of reducing sugars with a compound containing an amino group. AGEs bind to and trigger the receptor for AGEs (RAGE) through AGE-RAGE interaction, which is a major modulator of inflammation allied tumors. Dicarbonyls like, GO (glyoxal), MG (methylglyoxal) and 3-DG (3-deoxyglucosone) fashioned throughout lipid peroxidation, glycolysis, and protein degradation are viewed as key precursors of AGEs. These dicarbonyls lead to the carbonyl stress in living organisms, possibly resulting in carbonyl impairment of proteins, carbohydrates, DNA, and lipoproteins. The damage caused by carbonyls results in numerous lesions, some of which are involved in cancer pathogenesis. In this review, the effects of oxidative, carbonyl and glycative stress on cancer initiation and progression are thoroughly discussed, including probable signaling pathways and the effects on tumorigenesis.
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Affiliation(s)
- Saheem Ahmad
- IIRC-1 Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Biosciences, Integral University, Lucknow, India.
| | - Firoz Akhter
- IIRC-1 Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Pharmacology and Toxicology, Higuchi Biosciences Center, University of Kansas, KS, USA.
| | - Uzma Shahab
- Department of Biochemistry, King George Medical University, Lucknow, India
| | - Zeeshan Rafi
- Department of Bioengineering, Integral University, Lucknow, India
| | - Mohd Sajid Khan
- Department of Biosciences, Integral University, Lucknow, India
| | - Rabia Nabi
- Department of Biosciences, Integral University, Lucknow, India
| | | | - Khurshid Ahmad
- Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of South Korea
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27
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Deng R, Mo F, Chang B, Zhang Q, Ran H, Yang S, Zhu Z, Hu L, Su Q. Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade. Oncotarget 2017; 8:104216-104226. [PMID: 29262634 PMCID: PMC5732800 DOI: 10.18632/oncotarget.22185] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 07/25/2017] [Indexed: 12/01/2022] Open
Abstract
Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway.
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Affiliation(s)
- Ruyuan Deng
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Fengbo Mo
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Surgery and Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Bowen Chang
- Department of General Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Qi Zhang
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hui Ran
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shuhua Yang
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiqiang Zhu
- Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China
| | - Lei Hu
- Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China.,Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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28
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Chen H, Li Y, Zhu Y, Wu L, Meng J, Lin N, Yang D, Li M, Ding W, Tong X, Su Q. Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species. Medicine (Baltimore) 2017; 96:e7456. [PMID: 28816938 PMCID: PMC5571675 DOI: 10.1097/md.0000000000007456] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.
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Affiliation(s)
- Hanbei Chen
- Department of Endocrinology, Xinhua Hospital
| | - Yakui Li
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - Yemin Zhu
- Department of Endocrinology, Xinhua Hospital
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - Lifang Wu
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - Jian Meng
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - Ning Lin
- Department of Endocrinology, Xinhua Hospital
| | - Dianqiang Yang
- State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian
| | - Minle Li
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - WenJin Ding
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuemei Tong
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital
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29
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Abdul-Wahed A, Guilmeau S, Postic C. Sweet Sixteenth for ChREBP: Established Roles and Future Goals. Cell Metab 2017; 26:324-341. [PMID: 28768172 DOI: 10.1016/j.cmet.2017.07.004] [Citation(s) in RCA: 169] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 06/01/2017] [Accepted: 07/12/2017] [Indexed: 12/25/2022]
Abstract
With the identification of ChREBP in 2001, our interest in understanding the molecular control of carbohydrate sensing has surged. While ChREBP was initially studied as a master regulator of lipogenesis in liver and fat tissue, it is now clear that ChREBP functions as a central metabolic coordinator in a variety of cell types in response to environmental and hormonal signals, with wide implications in health and disease. Celebrating its sweet sixteenth birthday, we review here the current knowledge about the function and regulation of ChREBP throughout usual and less explored tissues, to recapitulate ChREBP's role as a whole-body glucose sensor.
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Affiliation(s)
- Aya Abdul-Wahed
- Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France
| | - Sandra Guilmeau
- Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France
| | - Catherine Postic
- Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
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30
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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Deng R, Wu H, Ran H, Kong X, Hu L, Wang X, Su Q. Glucose-derived AGEs promote migration and invasion of colorectal cancer by up-regulating Sp1 expression. Biochim Biophys Acta Gen Subj 2017; 1861:1065-1074. [PMID: 28237576 DOI: 10.1016/j.bbagen.2017.02.024] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 01/29/2017] [Accepted: 02/21/2017] [Indexed: 01/11/2023]
Abstract
It is well established that the risk of colorectal cancer (CRC) is significantly increased in diabetic patients. As one of main forms of the advanced glycation end products (AGEs) that accumulate in vivo, glucose-derived AGEs play an important role in the pathogenesis of diabetic complications and may contribute to CRC progression. However, to date, both the contribution of glucose-derived AGEs to the course of CRC and the underlying mechanism are unclear. In the present study, the concentration of glucose-derived AGEs in the serum and tumor tissue of patients with CRC increased. A clinical data analysis demonstrated that the expression of the receptor for AGEs (RAGE), Specificity Protein 1 (Sp1), and matrix metallopeptidase -2 (MMP2) was significantly higher in cancerous tissues compared with non-tumor tissue in Chinese Han patients with CRC and that RAGE expression was closely associated with lymph node metastasis and TNM stage. Furthermore, in vivo and in vitro experiments showed that AGEs promoted invasion and migration of colorectal cancer, and the AGEs treatment increased the expression of RAGE, Sp1, and MMP2 in a dose-dependent manner. A RAGE blocking antibody and an Sp1-specific siRNA attenuated the AGE-induced effects. Moreover, the AGEs treatment increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. In conclusion, glucose-derived AGEs promote the invasion and metastasis of CRC partially through the RAGE/ERK/SP1/MMP2 cascade. These findings may provide an explanation for the poor prognoses of colorectal cancer in diabetic patients.
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Affiliation(s)
- Ruyuan Deng
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China
| | - Huo Wu
- Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hui Ran
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China
| | - Xiang Kong
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China
| | - Lei Hu
- Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiao Wang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665, Kong Jiang Road, Shanghai 200092, China.
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Richards P, Ourabah S, Montagne J, Burnol AF, Postic C, Guilmeau S. MondoA/ChREBP: The usual suspects of transcriptional glucose sensing; Implication in pathophysiology. Metabolism 2017; 70:133-151. [PMID: 28403938 DOI: 10.1016/j.metabol.2017.01.033] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 01/21/2017] [Indexed: 12/22/2022]
Abstract
Identification of the Mondo glucose-responsive transcription factors family, including the MondoA and MondoB/ChREBP paralogs, has shed light on the mechanism whereby glucose affects gene transcription. They have clearly emerged, in recent years, as key mediators of glucose sensing by multiple cell types. MondoA and ChREBP have overlapping yet distinct expression profiles, which underlie their downstream targets and separate roles in regulating genes involved in glucose metabolism. MondoA can restrict glucose uptake and influences energy utilization in skeletal muscle, while ChREBP signals energy storage through de novo lipogenesis in liver and white adipose tissue. Because Mondo proteins mediate metabolic adaptations to changing glucose levels, a better understanding of cellular glucose sensing through Mondo proteins will likely uncover new therapeutic opportunities in the context of the imbalanced glucose homeostasis that accompanies metabolic diseases such as type 2 diabetes and cancer. Here, we provide an overview of structural homologies, transcriptional partners as well as the nutrient and hormonal mechanisms underlying Mondo proteins regulation. We next summarize their relative contribution to energy metabolism changes in physiological states and the evolutionary conservation of these pathways. Finally, we discuss their possible targeting in human pathologies.
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Affiliation(s)
- Paul Richards
- Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Sarah Ourabah
- Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Jacques Montagne
- Institut for Integrative Biology of the Cell (I2BC), CNRS, Université Paris-Sud, CEA, UMR 9198, F-91190, Gif-sur-Yvette, France
| | - Anne-Françoise Burnol
- Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Catherine Postic
- Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Sandra Guilmeau
- Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
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Cai B, Luo Y, Guo Q, Zhang X, Wu Z. A glucose-sensitive block glycopolymer hydrogel based on dynamic boronic ester bonds for insulin delivery. Carbohydr Res 2017; 445:32-39. [PMID: 28395252 DOI: 10.1016/j.carres.2017.04.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 03/18/2017] [Accepted: 04/05/2017] [Indexed: 12/01/2022]
Abstract
Hydrogels are good candidates to satisfy many needs for functional and tunable biomaterials. How to precisely control the gel structure and functions is crucial for the construction of sophisticated soft biomaterials comprising the hydrogels, which facilitates the impact of the surrounding environment on a unique biological function occurring. Here, glucose-responsive hydrogels comprised of 3-acrylamidophenyl boronic acid copolymerized with 2-lactobionamidoethyl methacrylate (p(APBA-b-LAMA)) were synthesized, and further evaluated as carriers for insulin delivery. The formation of (p(APBA-b-LAMA)) hydrogel was based on dynamic covalent bond using the association of boronic acid with diols. P(APBA-b-LAMA) hydrogel with the typical porous structure showed a rapid increase in equilibrium of swelling, which was up to 1856% after incubation with aqueous solution. Using insulin as a model protein therapeutic, p(APBA-b-LAMA) hydrogel exhibited high drug loading capability up to 15.6%, and also displayed glucose-dependent insulin release under physiological conditions. Additionally, the viability of NIH3T3 cells was more than 90% after treated with p(APBA-b-LAMA) hydrogel, indicating that the hydrogel had no cytotoxicity. Consequently, the novel p(APBA-b-LAMA) hydrogel has a practical application for diabetes treatment.
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Affiliation(s)
- Baoqi Cai
- The Xiyu Village Street Community Health Service Center in Hongqiao District, Tianjin, 300130, China
| | - Yanping Luo
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070, Tianjin, China
| | - Qianqian Guo
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, Nankai University, Tianjin, 300071, China
| | - Xinge Zhang
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, Nankai University, Tianjin, 300071, China
| | - Zhongming Wu
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070, Tianjin, China.
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Piperi C, Adamopoulos C, Papavassiliou AG. Potential of glycative stress targeting for cancer prevention. Cancer Lett 2017; 390:153-159. [PMID: 28111136 DOI: 10.1016/j.canlet.2017.01.020] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 01/10/2017] [Accepted: 01/11/2017] [Indexed: 12/15/2022]
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35
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González N, Prieto I, del Puerto-Nevado L, Portal-Nuñez S, Ardura JA, Corton M, Fernández-Fernández B, Aguilera O, Gomez-Guerrero C, Mas S, Moreno JA, Ruiz-Ortega M, Sanz AB, Sanchez-Niño MD, Rojo F, Vivanco F, Esbrit P, Ayuso C, Alvarez-Llamas G, Egido J, García-Foncillas J, Ortiz A, Diabetes Cancer Connect Consortium. 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications. Oncotarget 2017; 8:18456-18485. [PMID: 28060743 PMCID: PMC5392343 DOI: 10.18632/oncotarget.14472] [Citation(s) in RCA: 127] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 12/26/2016] [Indexed: 02/06/2023] Open
Abstract
Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer.
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Affiliation(s)
- Nieves González
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz-UAM, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
| | - Isabel Prieto
- Radiation Oncology, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Laura del Puerto-Nevado
- Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Sergio Portal-Nuñez
- Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Juan Antonio Ardura
- Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Marta Corton
- Genetics, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | | | - Oscar Aguilera
- Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | | | - Sebastián Mas
- Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | | | | | - Ana Belen Sanz
- Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
- REDINREN, Madrid, Spain
| | | | - Federico Rojo
- Pathology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | | | - Pedro Esbrit
- Bone and Mineral Metabolism laboratory, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Carmen Ayuso
- Genetics, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | | | - Jesús Egido
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz-UAM, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
- Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Jesús García-Foncillas
- Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
| | - Alberto Ortiz
- Nephrology, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain
- REDINREN, Madrid, Spain
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Identification of HNF-4α as a key transcription factor to promote ChREBP expression in response to glucose. Sci Rep 2016; 6:23944. [PMID: 27029511 PMCID: PMC4814918 DOI: 10.1038/srep23944] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 03/16/2016] [Indexed: 01/08/2023] Open
Abstract
Transcription factor carbohydrate responsive element binding protein (ChREBP) promotes glycolysis and lipogenesis in metabolic tissues and cancer cells. ChREBP-α and ChREBP-β, two isoforms of ChREBP transcribed from different promoters, are both transcriptionally induced by glucose. However, the mechanism by which glucose increases ChREBP mRNA levels remains unclear. Here we report that hepatocyte nuclear factor 4 alpha (HNF-4α) is a key transcription factor for glucose-induced ChREBP-α and ChREBP-β expression. Ectopic HNF-4α expression increased ChREBP transcription while knockdown of HNF-4α greatly reduced ChREBP mRNA levels in liver cancer cells and mouse primary hepatocytes. HNF-4α not only directly bound to an E-box-containing region in intron 12 of the ChREBP gene, but also promoted ChREBP-β transcription by directly binding to two DR1 sites and one E-box-containing site of the ChREBP-β promoter. Moreover, HNF-4α interacted with ChREBP-α and synergistically promoted ChREBP-β transcription. Functionally, HNF-4α suppression reduced glucose-dependent ChREBP induction. Increased nuclear abundance of HNF-4α and its binding to cis-elements of ChREBP gene in response to glucose contributed to glucose-responsive ChREBP transcription. Taken together, our results not only revealed the novel mechanism by which HNF-4α promoted ChREBP transcription in response to glucose, but also demonstrated that ChREBP-α and HNF-4α synergistically increased ChREBP-β transcription.
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Lin JA, Wu CH, Lu CC, Hsia SM, Yen GC. Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression. Mol Nutr Food Res 2016; 60:1850-64. [DOI: 10.1002/mnfr.201500759] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 12/11/2015] [Accepted: 01/07/2016] [Indexed: 12/15/2022]
Affiliation(s)
- Jer-An Lin
- Department of Food Science and Biotechnology; National Chung Hsing University; Taichung Taiwan
| | - Chi-Hao Wu
- School of Nutrition and Health Sciences; Taipei Medical University; Taipei Taiwan
| | - Chi-Cheng Lu
- Department of Food Science and Biotechnology; National Chung Hsing University; Taichung Taiwan
- School of Nutrition and Health Sciences; Taipei Medical University; Taipei Taiwan
| | - Shih-Min Hsia
- School of Nutrition and Health Sciences; Taipei Medical University; Taipei Taiwan
| | - Gow-Chin Yen
- Department of Food Science and Biotechnology; National Chung Hsing University; Taichung Taiwan
- Agricultural Biotechnology Center; National Chung Hsing University; Taichung Taiwan
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Lennicke C, Rahn J, Heimer N, Lichtenfels R, Wessjohann LA, Seliger B. Redox proteomics: Methods for the identification and enrichment of redox-modified proteins and their applications. Proteomics 2015; 16:197-213. [PMID: 26508685 DOI: 10.1002/pmic.201500268] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 09/14/2015] [Accepted: 10/15/2015] [Indexed: 01/24/2023]
Abstract
PTMs are defined as covalent additions to functional groups of amino acid residues in proteins like phosphorylation, glycosylation, S-nitrosylation, acetylation, methylation, lipidation, SUMOylation as well as oxidation. Oxidation of proteins has been characterized as a double-edged sword. While oxidative modifications, in particular of cysteine residues, are widely involved in the regulation of cellular homeostasis, oxidative stress resulting in the oxidation of biomolecules along with the disruption of their biological functions can be associated with the development of diseases, such as cancer, diabetes, and neurodegenerative diseases, respectively. This is also the case for advanced glycation end products, which result from chemical reactions of keto compounds such as oxidized sugars with proteins. The role of oxidative modifications under physiological and pathophysiological conditions remains largely unknown. Recently, novel technologies have been established that allow the enrichment, identification, and characterization of specific oxidative PTMs (oxPTMs). This is essential to develop strategies to prevent and treat diseases that are associated with oxidative stress. Therefore this review will focus on (i) the methods and technologies, which are currently applied for the detection, identification, and quantification of oxPTMs including the design of high throughput approaches and (ii) the analyses of oxPTMs related to physiological and pathological conditions.
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Affiliation(s)
- Claudia Lennicke
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
| | - Jette Rahn
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
| | - Nadine Heimer
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
| | - Rudolf Lichtenfels
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
| | | | - Barbara Seliger
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
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Kong SY, Takeuchi M, Hyogo H, McKeown-Eyssen G, Yamagishi SI, Chayama K, O'Brien PJ, Ferrari P, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Bastide N, Carbonnel F, Kühn T, Kaaks R, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Vasilopoulou E, Masala G, Pala V, Santucci De Magistris M, Tumino R, Naccarati A, Bueno-de-Mesquita HB, Peeters PH, Weiderpass E, Quirós JR, Jakszyn P, Sánchez MJ, Dorronsoro M, Gavrila D, Ardanaz E, Rutegård M, Nyström H, Wareham NJ, Khaw KT, Bradbury KE, Romieu I, Freisling H, Stavropoulou F, Gunter MJ, Cross AJ, Riboli E, Jenab M, Bruce WR. The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk. Cancer Epidemiol Biomarkers Prev 2015; 24:1855-63. [PMID: 26404963 PMCID: PMC6284787 DOI: 10.1158/1055-9965.epi-15-0422] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Accepted: 07/28/2015] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls from sugars such as glyceraldehyde. Glyceraldehyde contributes to the production of a group of compounds known as glyceraldehyde-derived advanced glycation end-products (glycer-AGEs), which may promote colorectal cancer through their proinflammatory and pro-oxidative properties. The objective of this study nested within a prospective cohort was to explore the association of circulating glycer-AGEs with risk of colorectal cancer. METHODS A total of 1,055 colorectal cancer cases (colon n = 659; rectal n = 396) were matchced (1:1) to control subjects. Circulating glycer-AGEs were measured by a competitive ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (95% CI), adjusting for potential confounding factors, including smoking, alcohol, physical activity, body mass index, and diabetes status. RESULTS Elevated glycer-AGEs levels were not associated with colorectal cancer risk (highest vs. lowest quartile, 1.10; 95% CI, 0.82-1.49). Subgroup analyses showed possible divergence by anatomical subsites (OR for colon cancer, 0.83; 95% CI, 0.57-1.22; OR for rectal cancer, 1.90; 95% CI, 1.14-3.19; Pheterogeneity = 0.14). CONCLUSIONS In this prospective study, circulating glycer-AGEs were not associated with risk of colon cancer, but showed a positive association with the risk of rectal cancer. IMPACT Further research is needed to clarify the role of toxic products of carbohydrate metabolism and energy excess in colorectal cancer development.
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Affiliation(s)
- So Yeon Kong
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Masayoshi Takeuchi
- Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | | | - Sho-Ichi Yamagishi
- Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Peter J O'Brien
- Department of Pharmacology, University of Toronto, Toronto, Canada
| | - Pietro Ferrari
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Anja Olsen
- Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Anne Tjønneland
- Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Marie-Christine Boutron-Ruault
- Lifestyle, Genes, and Health: Trans-generational Integrated Epidemiology, EMT, Institute Gustave Roussy, Villejuif, France
| | - Nadia Bastide
- Lifestyle, Genes, and Health: Trans-generational Integrated Epidemiology, EMT, Institute Gustave Roussy, Villejuif, France
| | - Franck Carbonnel
- Lifestyle, Genes, and Health: Trans-generational Integrated Epidemiology, EMT, Institute Gustave Roussy, Villejuif, France. Service d'hépato-gastroentérologie, Hôpital Bicetre, Le Kremlin-Bicêtre Cedex, France
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Krasimira Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
| | - Pagona Lagiou
- Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
| | - Effie Vasilopoulou
- Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece
| | - Giovanna Masala
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy
| | - Valeria Pala
- Epidemiology and Prevention Unit, IRCCS Foundation, National Cancer Institute, Milan, Italy
| | | | - Rosario Tumino
- Cancer Registry and Histopathology Unit, "Civic - MP Arezzo" Hospital, Ragusa, Italy
| | - Alessio Naccarati
- Human Genetics Foundation, Torino Molecular and Genetic Epidemiology Unit, Torino, Italy
| | - H B Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Epidemiology and Biostatistics, The School of Public Health, Imperil College London, London, United Kingdom. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Petra H Peeters
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatics, School of Public Health, Imperial College, London, United Kingdom
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway. Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Instituet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland
| | | | - Paula Jakszyn
- Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain
| | - María-José Sánchez
- CIBER Epidemiology and Public Health (CIBERESP), Spain. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - Miren Dorronsoro
- Public Health Direction and CIBERESP-Biodonostia Research Institute, Basque Regional Health Department, San Sebastian, Spain
| | - Diana Gavrila
- CIBER Epidemiology and Public Health (CIBERESP), Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
| | - Eva Ardanaz
- CIBER Epidemiology and Public Health (CIBERESP), Spain. Navarre Public Health Institute, Pamplona, Spain
| | - Martin Rutegård
- Department of Surgery, Department of Surgical and Perioperative Sciences, Umeå University, Sweden
| | - Hanna Nyström
- Department of Surgery, Department of Surgical and Perioperative Sciences, Umeå University, Sweden
| | - Nicholas J Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Kay-Tee Khaw
- Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom
| | - Kathryn E Bradbury
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Isabelle Romieu
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Heinz Freisling
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Faidra Stavropoulou
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Marc J Gunter
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
| | - W Robert Bruce
- Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
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Accumulation of advanced glycation end-products and activation of the SCAP/SREBP Lipogenetic pathway occur in diet-induced obese mouse skeletal muscle. PLoS One 2015; 10:e0119587. [PMID: 25750996 PMCID: PMC4353621 DOI: 10.1371/journal.pone.0119587] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 01/14/2015] [Indexed: 01/11/2023] Open
Abstract
Aim of this study was to investigate whether advanced glycation end-products (AGEs) accumulate in skeletal myofibers of two different animal models of diabesity and whether this accumulation could be associated to myosteatosis. Male C57Bl/6j mice and leptin-deficient ob/ob mice were divided into three groups and underwent 15 weeks of dietary manipulation: standard diet-fed C57 group (C57, n = 10), high-fat high-sugar diet-fed C57 group (HFHS, n = 10), and standard diet-fed ob/ob group (OB/OB, n = 8). HFHS mice and OB/OB mice developed glycometabolic abnormalities in association with decreased mass of the gastrocnemius muscle, fast-to-slow transition of muscle fibers, and lipid accumulation (that occurred preferentially in slow compared to fast fibers). Moreover, we found in muscle fibers of HFHS and OB/OB mice accumulation of AGEs that was preferential for the lipid-accumulating cells, increased expression of the lipogenic pathway SCAP/SREBP, and co-localisation between AGEs and SCAP-(hyper)expressing cells (suggestive for SCAP glycosylation). The increased expression of the SCAP/SREBP lipogenic pathway in muscle fibers is a possible mechanism underlying lipid accumulation and linking myosteatosis to muscle fiber atrophy and fast-to-slow transition that occur in response to diabesity.
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Yamagishi SI, Matsui T, Fukami K. Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Cancer Risk. Rejuvenation Res 2015; 18:48-56. [DOI: 10.1089/rej.2014.1625] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Sho-ichi Yamagishi
- Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
| | - Takanori Matsui
- Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
| | - Kei Fukami
- Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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