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Virchea LI, Frum A, Georgescu C, Pecsenye B, Máthé E, Mironescu M, Crăciunaș MT, Totan M, Tănăsescu C, Gligor FG. An Overview of the Bioactivity of Spontaneous Medicinal Plants Suitable for the Improvement of Lung Cancer Therapies. Pharmaceutics 2025; 17:336. [PMID: 40143000 PMCID: PMC11945085 DOI: 10.3390/pharmaceutics17030336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/26/2025] [Accepted: 03/03/2025] [Indexed: 03/28/2025] Open
Abstract
Lung cancer is the second cause of death in the world, being the most common type of cancer. Conventional therapies are not always recommended due to the particularities of patients. Thus, there is a need to develop new anticancer therapeutic agents. Medicinal plants constitute a source of bioactive compounds with therapeutic potential in lung cancer. The purpose of our narrative review is to evaluate and summarize the main studies on the cytotoxic effects of ten medicinal plants and their extracts, volatile oils, and bioactive compounds. We have also included studies that reported protective effects of these natural products against chemotherapy-induced toxicity. Studies were identified by assessing five databases using specific keywords. The investigated natural products possess cytotoxic effects on lung cancer cell cultures. Several mechanisms of action have been proposed including cell death by apoptosis, necrosis or autophagy, cell cycle arrest, the modulation of signaling pathways (PI3K/Akt and MAPK), the inhibition of migration, invasion and metastasis, antiangiogenesis, and targeting inflammation. Different bioactive compounds exhibit protective effects against chemotherapy-induced toxicity. Studies have shown promising results. To develop new therapeutic agents useful in treating lung cancer, the plants included in this review should be more deeply investigated to reveal their molecular mechanisms of action.
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Affiliation(s)
- Lidia-Ioana Virchea
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, Lucian Blaga Str. 2A, 550169 Sibiu, Romania; (L.-I.V.); (M.T.); (C.T.); (F.-G.G.)
| | - Adina Frum
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, Lucian Blaga Str. 2A, 550169 Sibiu, Romania; (L.-I.V.); (M.T.); (C.T.); (F.-G.G.)
| | - Cecilia Georgescu
- Faculty of Agriculture Sciences, Food Industry and Environmental Protection, “Lucian Blaga” University of Sibiu, Dr. Ion Rațiu Str. 7-9, 550012 Sibiu, Romania; (C.G.); (M.M.)
| | - Bence Pecsenye
- Institute of Nutrition Science, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Böszörményi Str. 128, 4032 Debrecen, Hungary; (B.P.); (E.M.)
| | - Endre Máthé
- Institute of Nutrition Science, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Böszörményi Str. 128, 4032 Debrecen, Hungary; (B.P.); (E.M.)
- Department of Life Sciences, Faculty of Medicine, Vasile Goldis, Western University from Arad, L. Rebreanu Str. 86, 310414 Arad, Romania
| | - Monica Mironescu
- Faculty of Agriculture Sciences, Food Industry and Environmental Protection, “Lucian Blaga” University of Sibiu, Dr. Ion Rațiu Str. 7-9, 550012 Sibiu, Romania; (C.G.); (M.M.)
| | - Mihai-Tudor Crăciunaș
- Faculty of Sciences, “Lucian Blaga” University of Sibiu, Dr. Ion Rațiu Str. 5-7, 550012 Sibiu, Romania;
| | - Maria Totan
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, Lucian Blaga Str. 2A, 550169 Sibiu, Romania; (L.-I.V.); (M.T.); (C.T.); (F.-G.G.)
| | - Ciprian Tănăsescu
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, Lucian Blaga Str. 2A, 550169 Sibiu, Romania; (L.-I.V.); (M.T.); (C.T.); (F.-G.G.)
| | - Felicia-Gabriela Gligor
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, Lucian Blaga Str. 2A, 550169 Sibiu, Romania; (L.-I.V.); (M.T.); (C.T.); (F.-G.G.)
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Yang Y, Huang L, Gao J, Qian B. Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress. Med Oncol 2024; 41:170. [PMID: 38847902 DOI: 10.1007/s12032-024-02413-6] [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: 04/16/2024] [Accepted: 05/23/2024] [Indexed: 07/03/2024]
Abstract
Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD+. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD+/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.
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Affiliation(s)
- Ye Yang
- Department of Pharmacology and Medicinal Chemistry, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, People's Republic of China
| | - Lei Huang
- Department of Pharmacology and Medicinal Chemistry, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, People's Republic of China
| | - Jie Gao
- Clinical Pharmacology Laboratory, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, 210004, Jiangsu, People's Republic of China
| | - Bingjun Qian
- Department of Pharmacology and Medicinal Chemistry, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, People's Republic of China.
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Bhimani J, O'Connell K, Kuk D, Du M, Navarro SL, Kantor ED. Glucosamine and Chondroitin Use and Mortality Among Adults in the United States from 1999 to 2014. JOURNAL OF INTEGRATIVE AND COMPLEMENTARY MEDICINE 2023; 29:492-500. [PMID: 36971848 PMCID: PMC10457612 DOI: 10.1089/jicm.2022.0783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Introduction: Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Results: Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). Conclusion: The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.
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Affiliation(s)
- Jenna Bhimani
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Deborah Kuk
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Inspire, Arlington, VA, USA
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sandi L. Navarro
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Elizabeth D. Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Pradhan P, Wen W, Cai H, Gao YT, Shu XO, Zheng W. Prospective Cohort Study of Ginseng Consumption in Association with Cancer Risk: Shanghai Women's Health Study. J Nutr 2023; 153:1170-1177. [PMID: 36863482 PMCID: PMC10356994 DOI: 10.1016/j.tjnut.2023.02.032] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 02/17/2023] [Accepted: 02/23/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Ginseng has been commonly used in Asian countries to promote longevity and health for >2000 years. Recent in vitro and in vivo studies, coupled with limited epidemiologic studies, have suggested that regular ginseng consumption may be related to lower cancer risk. OBJECTIVES We evaluated the association of ginseng consumption with risk of total and 15 site-specific cancers in a large cohort study conducted among Chinese women. Given the previous literature on ginseng consumption and cancer risk, we hypothesized that ginseng consumption might be associated with varying risks of cancer. METHODS This study included 65,732 female participants (mean age: 52.2 years) of the Shanghai Women's Health Study, an ongoing prospective cohort study. Baseline enrollment occurred between 1997 and 2000, and follow-up concluded on 31 December 2016. Ginseng use and covariates were assessed via an in-person interview conducted at the baseline recruitment. The cohort was followed for cancer incidence. Cox proportional hazard models were used to estimate HRs and 95% CIs for ginseng-cancer associations after adjusting for confounders. RESULTS During a mean 14.7 years of follow-up, 5067 incident cancer cases were identified. Overall, regular ginseng use was mostly not associated with risk of any site-specific cancer, or all cancers combined. Short-term (<3 years) ginseng use was found to be significantly associated with increased risk of liver cancer (HR = 1.71; 95% CI: 1.04, 2.79; P = 0.035), whereas long-term (≥3 years) ginseng use was found to be associated with increased risk of thyroid cancer (HR = 1.40; 95% CI: 1.02, 1.91; P = 0.036). Long-term ginseng use was found to be significantly associated with decreased risk of lymphatic and hematopoietic tissue malignancy (HR = 0.67; 95% CI: 0.46, 0.98; P = 0.039) and non-Hodgkin's lymphoma (HR = 0.57; 95% CI: 0.34, 0.97; P = 0.039). CONCLUSIONS This study provides suggestive evidence that ginseng consumption may be associated with risk of certain cancers.
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Affiliation(s)
- Pranoti Pradhan
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Wanqing Wen
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Hui Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Wei Zheng
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
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An Overview of Herbal Nutraceuticals, Their Extraction, Formulation, Therapeutic Effects and Potential Toxicity. SEPARATIONS 2023. [DOI: 10.3390/separations10030177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
Herbal nutraceuticals are foods derived from plants and/or their derivatives, such as oils, roots, seeds, berries, or flowers, that support wellness and combat acute and chronic ailments induced by unhealthful dietary habits. The current review enlists various traditional as well as unexplored herbs including angelica, burnet, caraway, laurel, parsley, yarrow, and zedoary, which are rich sources of bioactive components, such as aloesin, angelicin, trans-anethole, and cholesteric-7-en-3β-ol. The review further compares some of the extraction and purification techniques, namely, Soxhlet extraction, ultrasound assisted extraction, microwave assisted extraction, supercritical fluid extraction, accelerated solvent extraction, hydro-distillation extraction, ultra-high-pressure extraction, enzyme assisted extraction, pulsed electric field extraction, bio affinity chromatography, cell membrane chromatography, and ligand fishing. Herbal nutraceuticals can be purchased in varied formulations, such as capsules, pills, powders, liquids, and gels. Some of the formulations currently available on the market are discussed here. Further, the significance of herbal nutraceuticals in prevention and cure of diseases, such as diabetes, obesity, dementia, hypertension, and hypercholesterolemia; and as immunomodulators and antimicrobial agents has been discussed. Noteworthy, the inappropriate use of these herbal nutraceuticals can lead to hepatotoxicity, pulmonary toxicity, cytotoxicity, carcinogenicity, nephrotoxicity, hematotoxicity, and cardiac toxicity. Hence, this review concludes with a discussion of various regulatory aspects undertaken by the government agencies in order to minimize the adverse effects associated with herbal nutraceuticals.
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Cardile A, Zanrè V, Campagnari R, Asson F, Addo SS, Orlandi E, Menegazzi M. Hyperforin Elicits Cytostatic/Cytotoxic Activity in Human Melanoma Cell Lines, Inhibiting Pro-Survival NF-κB, STAT3, AP1 Transcription Factors and the Expression of Functional Proteins Involved in Mitochondrial and Cytosolic Metabolism. Int J Mol Sci 2023; 24:ijms24021263. [PMID: 36674794 PMCID: PMC9860844 DOI: 10.3390/ijms24021263] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/31/2022] [Accepted: 01/05/2023] [Indexed: 01/10/2023] Open
Abstract
Hyperforin (HPF), the main component responsible for the antidepressant action of Hypericum perforatum, displays additional beneficial properties including anti-inflammatory, antimicrobic, and antitumor activities. Among its antitumor effects, HPF activity on melanoma is poorly documented. Melanoma, especially BRAF-mutated melanoma, is still a high-mortality tumor type and the currently available therapies do not provide solutions. We investigated HPF's antimelanoma effectiveness in A375, FO1 and SK-Mel-28 human BRAF-mutated cell lines. Cell viability assays documented that all melanoma cells were affected by low HPF concentrations (EC50% 2-4 µM) in a time-dependent manner. A Br-deoxy-uridine incorporation assay attested a significant reduction of cell proliferation accompanied by decreased expression of cyclin D1 and A2, CDK4 and of the Rb protein phosphorylation, as assessed by immunoblots. In addition, the expression of P21/waf1 and the activated form of P53 were increased in A375 and SK-Mel-28 cells. Furthermore, HPF exerts cytotoxic effects. Apoptosis is induced 24 h after HPF administration, documented by an increase of cleaved-PARP1 and a decrease of both Bcl2 and Bcl-xL expression levels. Autophagy is induced, attested by an augmented LC3B expression and augmentation of the activated form of AMPK. Moreover, HPF lowers GPX4 enzyme expression, suggesting ferroptosis induction. HPF has been reported to activate the TRPC6 Ca++ channel and/or Ca++ and Zn++ release from mitochondria stores, increasing cytosolic Ca++ and Zn++ concentrations. Our data highlighted that HPF affects many cell-signaling pathways, including signaling induced by Ca++, such as FRA1, pcJun and pCREB, the expression or activity of which are increased shortly after treatment. However, the blockage of the TRPC6 Ca++ channel or the use of Ca++ and Zn++ chelators do not hinder HPF cytostatic/cytotoxic activity, suggesting that damages induced in melanoma cells may pass through other pathways. Remarkably, 24 h after HPF treatment, the expression of activated forms of the transcription factors NF-κB P65 subunit and STAT3 are significantly lowered. Several cytosolic (PGM2, LDHA and pPKM2) and mitochondrial (UQCRC1, COX4 and ATP5B) enzymes are downregulated by HPF treatment, suggesting a generalized reduction of vital functions in melanoma cells. In line with these results is the recognized ability of HPF to affect mitochondrial membrane potential by acting as a protonophore. Finally, HPF can hinder both melanoma cell migration and colony formation in soft agar. In conclusion, we provide evidence of the pleiotropic antitumor effects induced by HPF in melanoma cells.
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Affiliation(s)
- Alessia Cardile
- Section of Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
| | - Valentina Zanrè
- Section of Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
| | - Rachele Campagnari
- Section of Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
| | - Francesca Asson
- Section of Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
| | - Solomon Saforo Addo
- Section of Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
| | - Elisa Orlandi
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
| | - Marta Menegazzi
- Section of Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
- Correspondence:
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Liu B, Yang W, Zhang K. Role of Glucosamine and Chondroitin in the Prevention of Cancer: A Meta-Analysis. Nutr Cancer 2023; 75:785-794. [PMID: 36715012 DOI: 10.1080/01635581.2023.2173258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function of glucosamine and/or chondroitin intake against cancer risk. We searched the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR), corresponding to the 95% confidence interval (95% CI), was used to assess the association between chondroitin and/or glucosamine intake and cancer risk. Thirteen studies met the inclusion criteria, with 1,690,918 participants and 55,045 cancer cases. Overall, chondroitin and/or glucosamine intake was associated with a lower risk of colorectal cancer (OR = 0.91, 95% CI, 0.87-0.94) and lung cancer (OR = 0.84, 95% CI, 0.79-0.89). Subgroup analysis supported the protective effect of different SYSADOAs (chondroitin and/or glucosamine) intake. However, the protective effect was not observed in the only chondroitin intake group and in the NSAIDs group. Our meta-analysis found that the intake of glucosamine and/or chondroitin decreased the risk of colorectal and lung cancers. Moreover, NSAIDs use may have a synergistic protective effect.
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Affiliation(s)
- Bo Liu
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Wenxing Yang
- Department of Physiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Kui Zhang
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
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Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: a large prospective cohort study. Br J Nutr 2022; 128:721-732. [PMID: 34526168 PMCID: PMC9892851 DOI: 10.1017/s000711452100372x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
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Zhou Y, Li X, Luo W, Zhu J, Zhao J, Wang M, Sang L, Chang B, Wang B. Allicin in Digestive System Cancer: From Biological Effects to Clinical Treatment. Front Pharmacol 2022; 13:903259. [PMID: 35770084 PMCID: PMC9234177 DOI: 10.3389/fphar.2022.903259] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/23/2022] [Indexed: 12/24/2022] Open
Abstract
Allicin is the main active ingredient in freshly-crushed garlic and some other allium plants, and its anticancer effect on cancers of digestive system has been confirmed in many studies. The aim of this review is to summarize epidemiological studies and in vitro and in vivo investigations on the anticancer effects of allicin and its secondary metabolites, as well as their biological functions. In epidemiological studies of esophageal cancer, liver cancer, pancreatic cancer, and biliary tract cancer, the anticancer effect of garlic has been confirmed consistently. However, the results obtained from epidemiological studies in gastric cancer and colon cancer are inconsistent. In vitro studies demonstrated that allicin and its secondary metabolites play an antitumor role by inhibiting tumor cell proliferation, inducing apoptosis, controlling tumor invasion and metastasis, decreasing angiogenesis, suppressing Helicobacter pylori, enhancing the efficacy of chemotherapeutic drugs, and reducing the damage caused by chemotherapeutic drugs. In vivo studies further demonstrate that allicin and its secondary metabolites inhibit cancers of the digestive system. This review describes the mechanisms against cancers of digestive system and therapeutic potential of allicin and its secondary metabolites.
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Affiliation(s)
- Yang Zhou
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Second Clinical College, China Medical University, Shenyang, China
| | - Xingxuan Li
- The Second Clinical College, China Medical University, Shenyang, China
| | - Wenyu Luo
- The Second Clinical College, China Medical University, Shenyang, China
| | - Junfeng Zhu
- Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Bing Chang,
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
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Khan AA, Mannan V, Pervaiz MA, Akram A, Momin ES, Sanusi M, Kashyap T, Elshaikh AO. The Role of Glucosamine and Chondroitin Sulfate in the Prevention of Colorectal Cancer: A Systematic Review. Cureus 2022; 14:e25401. [PMID: 35774674 PMCID: PMC9236665 DOI: 10.7759/cureus.25401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/25/2022] [Indexed: 12/24/2022] Open
Abstract
Currently, colorectal cancer is the third most common cancer in the world. Recently, glucosamine and chondroitin have gained popularity for their beneficial effects on cancer. They have already been recognized for their therapeutic role in osteoarthritis. This systematic review aims to analyze the relationship between the combined consumption of glucosamine and chondroitin and the prevention of colorectal cancer. Three databases: PubMed, Google Scholar, and Science Direct, were searched to collect relevant articles. After screening full-text articles, seven studies were included in the systematic review. The review found a supportive association between glucosamine and chondroitin and the decreased incidence of colorectal cancer. Through an anti-inflammatory effect on the cell signaling pathway, the supplementation caused a reduction in colorectal cancer occurrence. The dose, frequency of usage of the supplement, and weight of individuals, along with the use of non-steroidal anti-inflammatory drugs, also affected the efficacy. To further assess this relationship, it is necessary to conduct double-blind, randomized controls trials for the supplements in cancer prevention and further explore their safety and efficacy with different ethnicities, drugs, doses, and weight individuals.
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Affiliation(s)
- Asma A Khan
- College of Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Vij Mannan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Muhammad Ahad Pervaiz
- Urology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aqsa Akram
- Internal Medicine, Dallah Hospital, Riyadh, SAU.,Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Elina S Momin
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.,Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand Municipal Medical College, Ahmedabad, IND
| | - Muhammad Sanusi
- Internal Medicine, Cardiology, Shenyang Medical College, Shenyang, CHN.,Internal Medicine, Cardiology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Tejasvi Kashyap
- General Practice, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Abeer O Elshaikh
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Zhang Q, Zhao Q, Shen Y, Zhao F, Zhu Y. Allium Vegetables, Garlic Supplements, and Risk of Cancer: A Systematic Review and Meta-Analysis. Front Nutr 2022; 8:746944. [PMID: 35402472 PMCID: PMC8985597 DOI: 10.3389/fnut.2021.746944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 12/21/2021] [Indexed: 11/13/2022] Open
Abstract
PurposeThe role of allium vegetables or garlic supplements on reducing cancer risk was inconsistent between laboratory study findings and related epidemiologic studies.MethodsStudies assessing the effect of allium vegetables and garlic supplement consumption on cancer risk were included in our meta-analysis. We used fixed- or random-effects models to pool effect measures to evaluate the highest and lowest consumption. A dose-response regression analysis was used to assess the association between allium vegetables, garlic supplements, and cancer risk.ResultsIn a pooled analysis of 22 studies with 25 reports on allium vegetables, a high consumption of allium vegetables showed no significant association with cancer risk (relative risk [RR] = 0.97, 95% confidence interval [CI] 0.92–1.03) in a fixed-effects model. Similarly, garlic supplements were not found to be significantly associated with an increased risk of cancer (RR = 0.97, 95% CI 0.84–1.12) in a random-effects model involving a pooled analysis of 10 studies with 11 reports. Consumption of allium vegetables did not significantly correspond with cancer risk (P for nonlinearity = 0.958, P for linearity = 0.907).ConclusionIn this meta-analysis, we found no evidence that higher consumption of allium vegetables or garlic supplements reduced the risk of cancer; however, this finding requires further validation.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021246947.
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Affiliation(s)
- Qifan Zhang
- Department of Neurology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Qing Zhao
- Department of Neurology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Yan Shen
- Department of Neurology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Fuping Zhao
- Department of Neurology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Yan Zhu
- Department of Pulmonary and Critical Care Medicine, Xi'an No.3 Hospital, Xi'an, China
- *Correspondence: Yan Zhu
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12
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Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/β-Catenin Signaling in HCT116 Colon Cancer Cells. Int J Mol Sci 2022; 23:ijms23062984. [PMID: 35328403 PMCID: PMC8954631 DOI: 10.3390/ijms23062984] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/25/2022] [Accepted: 03/08/2022] [Indexed: 12/30/2022] Open
Abstract
The therapeutic activities of natural plant extracts have been well known for centuries. Many of them, in addition to antiviral and antibiotic effects, turned out to have anti-tumor activities by targeting different signaling pathways. The canonical Wnt pathway represents a major tumorigenic pathway deregulated in numerous tumor entities, including colon cancer. Here, we investigated the acylphloroglucinols hyperforin (HF) from St. John's wort (Hypericum perforatum L.) and myrtucommulone A (MC A) from myrtle (Myrtus communis) and semi-synthetic derivatives thereof (HM 177, HM 297, HM298) for their effects on Wnt/β-catenin signaling. None of these substances revealed major cytotoxicity on STF293 embryonic kidney and HCT116 colon carcinoma cells at concentrations up to 10 μM. At this concentration, HF and HM 177 showed the strongest effect on cell proliferation, whereas MC A and HM 177 most prominently inhibited anchorage-independent growth of HCT116 cells. Western blot analyses of active β-catenin and β-catenin/TCF reporter gene assays in STF293 cells revealed inhibitory activities of HF, MC A and HM 177. In line with this, the expression of endogenous Wnt target genes, Axin and Sp5, in HCT116 cells was significantly reduced. Our data suggest that the acylphloroglucinols hyperforin, myrtucommulone A and its derivative HM 177 represent potential new therapeutic agents to inhibit Wnt/β-catenin signaling in colon cancer.
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13
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Kantor ED, O'Connell K, Liang PS, Navarro SL, Giovannucci EL, Du M. Glucosamine Use and Risk of Colorectal Cancer: Results from UK Biobank. Cancer Epidemiol Biomarkers Prev 2022; 31:647-653. [PMID: 35027430 DOI: 10.1158/1055-9965.epi-21-1171] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/29/2021] [Accepted: 01/12/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Use of the dietary supplement glucosamine has been associated with reduced risk of colorectal cancer (CRC); however, it remains unclear if the association varies by screening status, time, and other factors. METHODS We therefore evaluated these questions in UK Biobank. Multivariable-adjusted Hazard Ratios (HRs) and 95% Confidence Intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS No association was observed between use of glucosamine and risk of CRC overall (HR: 0.94; 95% CI: 0.85-1.04). However, the association varied by screening status (p-interaction:0.05), with an inverse association observed only among never-screened individuals (HR: 0.86; 95% CI: 0.76-0.98). When stratified by study time, an inverse association was observed in early follow-up among those entering the cohort in early years (2006-2008, HR: 0.80; 95% CI: 0.67-0.95). No heterogeneity was observed by age, sex, body mass index, smoking status, or use of non-steroidal anti-inflammatory drugs. CONCLUSIONS While there was no association between glucosamine use and CRC overall, the inverse association among never-screened individuals mirrors our observations in prior exploratory analyses of US cohorts. The National Health Service Bowel Cancer Screening Program started in 2006 in England and was more widely implemented across the UK by 2009. In line with this, we observed an inverse association limited to early follow-up in those surveyed 2006-2008, before screening was widely implemented. IMPACT These data suggest that unscreened individuals may benefit from use of glucosamine; however, further studies are needed to confirm the interplay of screening and timing.
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Affiliation(s)
- Elizabeth D Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
| | - Peter S Liang
- Medicine, Division of Gastroenterology and Hepatology, NYU Langone Health
| | - Sandi L Navarro
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center
| | | | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
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14
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Lee J, Zhao N, Fu Z, Choi J, Lee HJ, Chung M. Effects of garlic intake on cancer: a systematic review of randomized clinical trials and cohort studies. Nutr Res Pract 2021; 15:773-788. [PMID: 34858554 PMCID: PMC8601942 DOI: 10.4162/nrp.2021.15.6.773] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/14/2021] [Accepted: 07/21/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/OBJECTIVES Due to the rapid increase of global cancer incidence and mortality and a high level of interest in cancer prevention, a systematic review of garlic intake and cancer risk is needed. SUBJECTS/METHODS We implemented a systematic review to examine the effects of varying levels of garlic intake on cancer. We conducted comprehensive literature searches in three electronic databases (MEDLINE, Embase, and Web of Science) for studies published between database inception and July or September of 2018. Two investigators independently screened abstracts and full-texts, extracted data, and assessed risk of bias (RoB). A total of one medium-quality randomized controlled trial (RCT) and 13 cohort studies graded as high RoB were included. RESULTS The 1-year follow-up results from a RCT showed that a significant decrease in the number and size of colorectal adenomas among participants with colorectal adenomas who received high-dose aged garlic extract (AGE) compared with those who received low-dose AGE (P < 0.05). The results of prospective observational studies provided inconsistent associations of colorectal cancer risk with garlic supplements and garlic intake as food. CONCLUSIONS In summary, the AGE was effective in reducing the number and magnitude of colorectal adenomas in one RCT, but there were inconsistent associations between garlic intake and colorectal cancer in cohort studies. Therefore, we could not draw a firm conclusion regarding the effects of garlic on cancer, because the current strength of evidence is inadequate due to a lack of number of high-quality RCTs.
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Affiliation(s)
- Jounghee Lee
- Department of Food and Nutrition, Kunsan National University, Gunsan 54150, Korea
| | - Naisi Zhao
- Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, MA 02111, USA
| | - Zhuxuan Fu
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA
| | - Jihee Choi
- Department of Food and Nutrition, Gachon University, Seongnam 13120, Korea
| | - Hae-Jeung Lee
- Department of Food and Nutrition, Gachon University, Seongnam 13120, Korea
| | - Mei Chung
- Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, MA 02111, USA
- Division of Nutrition Epidemiology and Data Science, Freidman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA
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Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F. Caloric Restriction Mimetics in Nutrition and Clinical Trials. Front Nutr 2021; 8:717343. [PMID: 34552954 PMCID: PMC8450594 DOI: 10.3389/fnut.2021.717343] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/13/2021] [Indexed: 12/29/2022] Open
Abstract
The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.
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Affiliation(s)
- Sebastian J. Hofer
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
- Field of Excellence BioHealth, University of Graz, Graz, Austria
| | - Sergio Davinelli
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Martina Bergmann
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
| | - Giovanni Scapagnini
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Frank Madeo
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
- Field of Excellence BioHealth, University of Graz, Graz, Austria
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16
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Moon JM, Finnegan P, Stecker RA, Lee H, Ratliff KM, Jäger R, Purpura M, Slupsky CM, Marco ML, Wissent CJ, Theodosakis J, Kerksick CM. Impact of Glucosamine Supplementation on Gut Health. Nutrients 2021; 13:2180. [PMID: 34202877 PMCID: PMC8308242 DOI: 10.3390/nu13072180] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 11/16/2022] Open
Abstract
Glucosamine (GLU) is a natural compound found in cartilage, and supplementation with glucosamine has been shown to improve joint heath and has been linked to reduced mortality rates. GLU is poorly absorbed and may exhibit functional properties in the gut. The purpose of this study was to examine the impact of glucosamine on gastrointestinal function as well as changes in fecal microbiota and metabolome. Healthy males (n = 6) and females (n = 5) (33.4 ± 7.7 years, 174.1 ± 12.0 cm, 76.5 ± 12.9 kg, 25.2 ± 3.1 kg/m2, n = 11) completed two supplementation protocols that each spanned three weeks separated by a washout period that lasted two weeks. In a randomized, double-blind, placebo-controlled, crossover fashion, participants ingested a daily dose of GLU hydrochloride (3000 mg GlucosaGreen®, TSI Group Ltd., Missoula, MT, USA) or maltodextrin placebo. Study participants completed bowel habit and gastrointestinal symptoms questionnaires in addition to providing a stool sample that was analyzed for fecal microbiota and metabolome at baseline and after the completion of each supplementation period. GLU significantly reduced stomach bloating and showed a trend towards reducing constipation and hard stools. Phylogenetic diversity (Faith's PD) and proportions of Pseudomonadaceae, Peptococcaceae, and Bacillaceae were significantly reduced following GLU consumption. GLU supplementation significantly reduced individual, total branched-chain, and total amino acid excretion, with no glucosamine being detected in any of the fecal samples. GLU had no effect on fecal short-chain fatty acids levels. GLU supplementation provided functional gut health benefits and induced fecal microbiota and metabolome changes.
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Affiliation(s)
- Jessica M. Moon
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
| | - Peter Finnegan
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
| | - Richard A. Stecker
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
| | - Hanna Lee
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
| | - Kayla M. Ratliff
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
| | - Ralf Jäger
- Increnovo, LLC, Milwaukee, WI 53202, USA;
| | - Martin Purpura
- Department of Nutrition, University of California, Davis, CA 95616, USA;
| | - Carolyn M. Slupsky
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
- Department of Nutrition, University of California, Davis, CA 95616, USA;
| | - Maria L. Marco
- Department of Food Science & Technology, University of California, Davis, CA 95616, USA; (P.F.); (H.L.); (C.M.S.); (M.L.M.)
| | | | | | - Chad M. Kerksick
- Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO 63301, USA; (J.M.M.); (R.A.S.); (K.M.R.)
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17
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Farhat Z, Hershberger PA, Freudenheim JL, Mammen MJ, Hageman Blair R, Aga DS, Mu L. Types of garlic and their anticancer and antioxidant activity: a review of the epidemiologic and experimental evidence. Eur J Nutr 2021; 60:3585-3609. [PMID: 33543365 DOI: 10.1007/s00394-021-02482-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 01/08/2021] [Indexed: 02/07/2023]
Abstract
Garlic, an Allium vegetable, contains rich flavonoids organosulfur compounds (OSCs) that have potent anticancer properties. The aim of the review is to provide an overview of the different types of garlic, their active compounds, and the potential anticancer benefits with a focus on antioxidant activity. Animal and cell line studies have provided convincing evidence that garlic and its organosulfur compounds inhibit carcinogenesis through a number of events including induction of apoptosis, inhibiting cellular proliferation, scavenging radical oxygen species (ROS), increasing the activities of enzymes such as glutathione S-transferase, and reducing tumor size. Epidemiological studies showed compelling evidence that garlic consumption is associated with decreased risk of colorectal cancer, but inconsistent evidence for stomach, breast, and prostate cancers. Studies also suggest that the presence and potency of garlic OSCs varies with respect to the preparation and form of garlic. Further epidemiological studies with information on garlic form consumed or preparation methods and molecular studies regarding its antioxidant mechanisms, such as increasing enzymatic and nonenzymatic antioxidants levels, are warranted.
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Affiliation(s)
- Zeinab Farhat
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Pamela A Hershberger
- Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Jo L Freudenheim
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Manoj J Mammen
- Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Rachael Hageman Blair
- Department of Biostatistics, University at Buffalo, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Diana S Aga
- Department of Chemistry, College of Arts and Sciences, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Lina Mu
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA.
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18
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Kantor ED, O'Connell K, Du M, Cao C, Zhang X, Lee DH, Cao Y, Giovannucci EL. Glucosamine and Chondroitin Use in Relation to C-Reactive Protein Concentration: Results by Supplement Form, Formulation, and Dose. J Altern Complement Med 2021; 27:150-159. [PMID: 33290138 PMCID: PMC7891193 DOI: 10.1089/acm.2020.0283] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Objectives: Glucosamine and chondroitin supplements have been associated with reduced inflammation, as measured by C-reactive protein (CRP). It is unclear if associations vary by formulation (glucosamine alone vs. glucosamine+chondroitin), form (glucosamine hydrochloride vs. glucosamine sulfate), or dose. Design, Subjects, Setting, Location: The authors evaluated these questions using cross-sectional data collected between 1999 and 2010 on 21,917 US adults, surveyed as part of the National Health and Nutrition Examination Survey (NHANES). Exposures: Glucosamine and chondroitin use was assessed during an in-home interview; exposures include supplement formulation, form, and dose. Outcome/Analysis: CRP was measured using blood collected at interview. Survey-weighted linear regression was used to evaluate the multivariable-adjusted association between exposures and log-transformed CRP. Results: In early years (1999-2004), use of glucosamine (ratio = 0.87; 95% confidence interval [CI] = 0.79-0.96) and chondroitin (ratio = 0.83; 95% CI = 0.72-0.95) was associated with reduced CRP. However, associations significantly varied by calendar time (p-interaction = 0.04 and p-interaction = 0.01, respectively), with associations nonsignificant in later years (ratio = 1.09; 95% CI = 0.94-1.28 and ratio = 1.16; 95% CI = 0.99-1.35, respectively). Consequently, all analyses have been stratified by calendar time. Associations did not significantly differ by formulation in either set of years; however, significant associations were observed for combined use of glucosamine+chondroitin (ratioearly = 0.82; 95% CI = 0.72-0.95; ratiolate = 1.16; 1.00-1.35), but not glucosamine alone. Associations also did not significantly differ by supplement form. Even so, a significant inverse association was observed only for glucosamine sulfate in the early years (ratio = 0.78; 95% CI = 0.64-0.95); no significant association was observed for glucosamine hydrochloride. No significant trends were observed by dose. Conclusions: Although a significant inverse association was observed for glucosamine and chondroitin and CRP in early years, this association did not hold in later years. This pattern held for combined use of glucosamine+chondroitin as well as glucosamine sulfate, although associations did not significantly vary by supplement form, formulation, or dose. Further study is needed to better understand these associations in the context of calendar time.
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Affiliation(s)
- Elizabeth D. Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Chao Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, St. Louis, MO, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Dong Hoon Lee
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, St Louis, MO, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, St Louis, MO, USA
| | - Edward L. Giovannucci
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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19
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Menegazzi M, Masiello P, Novelli M. Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics. Antioxidants (Basel) 2020; 10:antiox10010018. [PMID: 33379141 PMCID: PMC7824709 DOI: 10.3390/antiox10010018] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/17/2020] [Accepted: 12/21/2020] [Indexed: 12/12/2022] Open
Abstract
In this paper we review the mechanisms of the antitumor effects of Hypericum perforatum L. (St. John's wort, SJW) and its main active component hyperforin (HPF). SJW extract is commonly employed as antidepressant due to its ability to inhibit monoamine neurotransmitters re-uptake. Moreover, further biological properties make this vegetal extract very suitable for both prevention and treatment of several diseases, including cancer. Regular use of SJW reduces colorectal cancer risk in humans and prevents genotoxic effects of carcinogens in animal models. In established cancer, SJW and HPF can still exert therapeutic effects by their ability to downregulate inflammatory mediators and inhibit pro-survival kinases, angiogenic factors and extracellular matrix proteases, thereby counteracting tumor growth and spread. Remarkably, the mechanisms of action of SJW and HPF include their ability to decrease ROS production and restore pH imbalance in tumor cells. The SJW component HPF, due to its high lipophilicity and mild acidity, accumulates in membranes and acts as a protonophore that hinders inner mitochondrial membrane hyperpolarization, inhibiting mitochondrial ROS generation and consequently tumor cell proliferation. At the plasma membrane level, HPF prevents cytosol alkalization and extracellular acidification by allowing protons to re-enter the cells. These effects can revert or at least attenuate cancer cell phenotype, contributing to hamper proliferation, neo-angiogenesis and metastatic dissemination. Furthermore, several studies report that in tumor cells SJW and HPF, mainly at high concentrations, induce the mitochondrial apoptosis pathway, likely by collapsing the mitochondrial membrane potential. Based on these mechanisms, we highlight the SJW/HPF remarkable potentiality in cancer prevention and treatment.
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Affiliation(s)
- Marta Menegazzi
- Department of Neuroscience, Biomedicine and Movement Sciences, Biochemistry Section, School of Medicine, University of Verona, Strada Le Grazie 8, I-37134 Verona, Italy
- Correspondence: ; Tel.: +39-045-802-7168
| | - Pellegrino Masiello
- Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Via Roma 55, I-56126 Pisa, Italy; (P.M.); (M.N.)
| | - Michela Novelli
- Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Via Roma 55, I-56126 Pisa, Italy; (P.M.); (M.N.)
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20
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Novelli M, Masiello P, Beffy P, Menegazzi M. Protective Role of St. John's Wort and Its Components Hyperforin and Hypericin against Diabetes through Inhibition of Inflammatory Signaling: Evidence from In Vitro and In Vivo Studies. Int J Mol Sci 2020; 21:E8108. [PMID: 33143088 PMCID: PMC7662691 DOI: 10.3390/ijms21218108] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/26/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus is a very common chronic disease with progressively increasing prevalence. Besides the well-known autoimmune and inflammatory pathogenesis of type 1 diabetes, in many people, metabolic changes and inappropriate lifestyle favor a subtle chronic inflammatory state that contributes to development of insulin resistance and progressive loss of β-cell function and mass, eventually resulting in metabolic syndrome or overt type 2 diabetes. In this paper, we review the anti-inflammatory effects of the extract of Hypericum perforatum L. (St. John's wort, SJW) and its main active ingredients firstly in representative pathological situations on inflammatory basis and then in pancreatic β cells and in obese or diabetic animal models. The simultaneous and long-lasting inhibition of signal transducer and activator of transcription (STAT)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs)/c-jun N-terminal kinase (JNK) signaling pathways involved in pro-inflammatory cytokine-induced β-cell dysfunction/death and insulin resistance make SJW particularly suitable for both preventive and therapeutic use in metabolic diseases. Hindrance of inflammatory cytokine signaling is likely dependent on the hyperforin content of SJW extract, but recent data reveal that hypericin can also exert relevant protective effects, mediated by activation of the cyclic adenosine monophosphate (cAMP)/protein kinase cAMP-dependent (PKA)/adenosine monophosphate activated protein kinase (AMPK) pathway, against high-fat-diet-induced metabolic abnormalities. Actually, the mechanisms of action of the two main components of SJW appear complementary, strengthening the efficacy of the plant extract. Careful quantitative analysis of SJW components and suitable dosage, with monitoring of possible drug-drug interaction in a context of remarkable tolerability, are easily achievable pre-requisites for forthcoming clinical applications.
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Affiliation(s)
- Michela Novelli
- Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, 56126 Pisa, Italy
| | - Pellegrino Masiello
- Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, 56126 Pisa, Italy
| | - Pascale Beffy
- Institute of Clinical Physiology, CNR, 56124 Pisa, Italy;
| | - Marta Menegazzi
- Department of Neuroscience, Biomedicine and Movement Sciences, Biochemistry Section, School of Medicine, University of Verona, 37134 Verona, Italy;
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Lee DH, Cao C, Zong X, Zhang X, O'Connell K, Song M, Wu K, Du M, Cao Y, Giovannucci EL, Kantor ED. Glucosamine and Chondroitin Supplements and Risk of Colorectal Adenoma and Serrated Polyp. Cancer Epidemiol Biomarkers Prev 2020; 29:2693-2701. [PMID: 33055203 DOI: 10.1158/1055-9965.epi-20-0805] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 08/17/2020] [Accepted: 09/22/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. METHODS Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS), and NHS2 who reported on glucosamine/chondroitin use in 2002 and who subsequently underwent ≥1 lower gastrointestinal endoscopy. By 2012, 5,715 conventional (2,016 high-risk) adenomas were detected, as were 4,954 serrated polyps. Multivariable logistic regression for clustered data was used to calculate OR and 95% confidence intervals (CI). RESULTS Glucosamine/chondroitin use was inversely associated with high risk and any conventional adenoma in NHS and HPFS: in the pooled multivariable-adjusted model, glucosamine + chondroitin use at baseline was associated with a 26% (OR = 0.74; 95% CI, 0.60-0.90; P heterogeneity = 0.23) and a 10% (OR = 0.90; 95% CI, 0.81-0.99; P heterogeneity = 0.36) lower risk of high-risk adenoma and overall conventional adenoma, respectively. However, no association was observed in NHS2, a study of younger women (high-risk adenoma: OR = 1.09; 95% CI, 0.82-1.45; overall conventional adenoma: OR = 1.00; 95% CI, 0.86-1.17), and effect estimates pooled across all three studies were not significant (high-risk: OR = 0.83; 95% CI, 0.63-1.10; P heterogeneity = 0.03; overall conventional adenoma: OR = 0.93; 95% CI, 0.85-1.02; P heterogeneity = 0.31). No associations were observed for serrated polyps. CONCLUSIONS Glucosamine/chondroitin use was associated with lower risks of high-risk and overall conventional adenoma in older adults; however, this association did not hold in younger women, or for serrated polyps. IMPACT Our study suggests that glucosamine and chondroitin may act on early colorectal carcinogenesis in older adults.
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Affiliation(s)
- Dong Hoon Lee
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
| | - Chao Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Xiaoyu Zong
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kelli O'Connell
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Elizabeth D Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
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Ibáñez-Sanz G, Guinó E, Morros R, Quijada-Manuitt MÁ, de la Peña-Negro LC, Moreno V. Chondroitin Sulphate and Glucosamine Use Depend on Nonsteroidal Anti-inflammatory Drug Use to Modify the Risk for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 2020; 29:1809-1816. [PMID: 32651216 DOI: 10.1158/1055-9965.epi-19-1051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 11/22/2019] [Accepted: 06/24/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND A safe and effective colorectal cancer chemoprevention agent remains to be discovered. There is little evidence regarding the protective effect of chondroitin sulphate and glucosamine on colorectal cancer. We aimed to assess the association between colorectal cancer risk and the use of chondroitin sulphate and glucosamine using a large cohort with dispensed data. METHODS We performed a population-based case-control study in Catalonia using primary care reimbursed medication records (SIDIAP database). The study included 25,811 cases with an incident diagnosis of colorectal cancer and 129,117 matched controls between 2010 and 2015. RESULTS The prevalence of ever use was 9.0% (n = 13,878) for chondroitin sulphate, 7.3% (n = 11,374) for glucosamine, and 35% for regular use of nonsteroidal anti-inflammatory drugs (NSAID; n = 45,774). A decreased risk of colorectal cancer was observed among chondroitin sulphate use [OR: 0.96; 95% confidence interval (CI), 0.91-1.01], glucosamine use (OR: 0.92; 95% CI, 0.87-0.97), and concurrent use of chondroitin sulphate and glucosamine (OR: 0.83; 95% CI, 0.70-0.98). Especially for glucosamine, there was a dose-response association regarding duration and cumulative dose. The analysis stratified by simultaneous use with other NSAIDs showed that these drugs used without other NSAIDs do not reduce risk (OR: 1.06; 95% CI, 0.74-1.51). However, they may have a synergistic protective effect when used with other NSAIDs (OR: 0.80; 95% CI, 0.72-0.88). CONCLUSIONS This study does not provide strong support for an independent protective association of chondroitin sulphate or glucosamine on colorectal cancer risk in our population. However, these drugs may have a synergistic beneficial effect among NSAID users. IMPACT Chondroitin sulphate or glucosamine may contribute to the protective effect of NSAID use in colorectal cancer.
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Affiliation(s)
- Gemma Ibáñez-Sanz
- Oncology Data Analytics Program, Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain
- Servei d'Aparell Digestiu, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
- Colorectal Cancer Group, programa ONCOBELL, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Elisabet Guinó
- Oncology Data Analytics Program, Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain
- Colorectal Cancer Group, programa ONCOBELL, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Rosa Morros
- Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Barcelona, Spain
- Institut Català de la Salut (ICS), Girona, Spain
- Fundació Institut Universitari per a la Recerca en Atenció Primària de Salut Jordi Gol i Gurina (IDIAP Jordi Gol), Barcelona, Spain
| | - María Ángeles Quijada-Manuitt
- Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Departament de Patologia i Terapèutica Experimental, Unitat Docent Campus de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Luisa Carmen de la Peña-Negro
- Oncology Data Analytics Program, Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain
- Servei d'Aparell Digestiu, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
- Servei d'Aparell Digestiu, Hospital de Viladecans, Viladecans, Spain
| | - Victor Moreno
- Oncology Data Analytics Program, Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain.
- Colorectal Cancer Group, programa ONCOBELL, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Department de Ciències clíniques, Facultat de medicina i Ciències de la salut, Universitat de Barcelona, Barcelona, Spain
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Khan AR, Yang X, Du X, Yang H, Liu Y, Khan AQ, Zhai G. Chondroitin sulfate derived theranostic and therapeutic nanocarriers for tumor-targeted drug delivery. Carbohydr Polym 2020; 233:115837. [PMID: 32059890 DOI: 10.1016/j.carbpol.2020.115837] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 12/22/2019] [Accepted: 01/06/2020] [Indexed: 12/11/2022]
Abstract
The standard chemotherapy is facing the challenges of lack of cancer selectivity and development of drug resistance. Currently, with the application of nanotechnology, the rationally designed nanocarriers of chondroitin sulfate (CS) have been fabricated and their unique features of low toxicity, biocompatibility, and active and passive targeting made them drug delivery vehicles of the choice for cancer therapy. The hydrophilic and anionic CS could be incorporated as a building block into- or decorated on the surface of nanoformulations. Micellar nanoparticles (NPs) self-assembled from amphiphilic CS-drug conjugates and CS-polymer conjugates, polyelectrolyte complexes (PECs) and nanogels of CS have been widely implicated in cancer directed therapy. The surface modulation of organic, inorganic, lipid and metallic NPs with CS promotes the receptor-mediated internalization of NPs to the tumor cells. The potential contribution of CS and CS-proteoglycans (CSPGs) in the pathogenesis of various cancer types, and CS nanocarriers in immunotherapy, radiotherapy, sonodynamic therapy (SDT) and photodynamic therapy (PDT) of cancer are summarized in this review paper.
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Affiliation(s)
- Abdur Rauf Khan
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China
| | - Xiaoye Yang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China
| | - Xiyou Du
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China
| | - Haotong Yang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China
| | - Yuanxiu Liu
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China
| | - Abdul Qayyum Khan
- Pakistan Council of Scientific and Industrial Research, Lahore, Pakistan
| | - Guangxi Zhai
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China.
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Abstract
This was a meta-analysis of epidemiological articles that aimed to estimate the association of garlic intake with the risk of colorectal cancer (CRC).Electronic databases, including the Cochrane Database of Systematic Reviews, PubMed, and EMBASE, were systemically searched from inception to May 2019 to identify related articles. In addition, a random model was used to pool the included evidence based on heterogeneity. Additionally, subgroup analyses were carried out to examine the differences between different groups. The stability of our findings was tested through sensitivity analyses. Publication bias was also assessed by Egger and Begg tests. Moreover, all enrolled studies were ordered according to the publication year for a cumulative meta-analysis.A total of 11 studies (involving 12,558 cases) were included in the current meta-analysis. Our integrated relative risk (RR) of CRC was 0.80 (95% confidence interval [CI], 0.69-0.91) for the highest versus the lowest garlic consumption categories (RR: 0.71 [95% CI, 0.60-0.84] for controls and RR: 0.99 [95% CI, 0.80-1.23] for cohorts). There was significant heterogeneity across all enrolled studies (I = 68.3%, P < .01). The sensitivity analysis revealed no notable alterations of the integrated results. According to the funnel plot regarding garlic intake and the risk of CRC, together with the Egger test (P = .1) and Begg test (P = .064) results, there was no notable evidence of publication bias. The cumulative meta-analysis suggested that the 95% CIs became narrower with the increase in sample size.Based on the existing evidence, garlic intake could reduce the risk of CRC.
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Affiliation(s)
- Xi Zhou
- Department of Anorectal Surgery, Nanjing University of Chinese Medicine
| | - Haihua Qian
- Department of Anorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Dan Zhang
- Department of Anorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Li Zeng
- Department of Anorectal Surgery, Nanjing University of Chinese Medicine
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25
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Navarro SL, Levy L, Curtis KR, Lampe JW, Hullar MA. Modulation of Gut Microbiota by Glucosamine and Chondroitin in a Randomized, Double-Blind Pilot Trial in Humans. Microorganisms 2019; 7:microorganisms7120610. [PMID: 31771179 PMCID: PMC6956221 DOI: 10.3390/microorganisms7120610] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 11/16/2019] [Accepted: 11/22/2019] [Indexed: 12/18/2022] Open
Abstract
Glucosamine and chondroitin (G&C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology. G&C are poorly absorbed and therefore metabolized by gut microbiota. G&C have been associated with changes in microbial structure, which may alter host response. We conducted a randomized, double-blind, placebo-controlled crossover trial in ten healthy adults to evaluate the effects of a common dose of G&C compared to placebo for 14 days on gut microbial community structure, measured by 16S rRNA gene sequencing. Linear mixed models were used to evaluate the effect of G&C compared to placebo on fecal microbial alpha and beta diversity, seven phyla, and 137 genera. Nine genera were significantly different between interventions (False Discovery Rate < 0.05). Abundances of four Lachnospiraceae genera, two Prevotellaceae genera, and Desulfovibrio were increased after G&C compared to placebo, while Bifidobacterium and a member of the Christensenellaceae family were decreased. Our results suggest that G&C affect the composition of the gut microbiome which may have implications for therapeutic efficacy.
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Affiliation(s)
- Sandi L. Navarro
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (L.L.); (K.R.C.); (J.W.L.)
- Correspondence: ; Tel.: +1-206-667-6583
| | - Lisa Levy
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (L.L.); (K.R.C.); (J.W.L.)
| | - Keith R. Curtis
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (L.L.); (K.R.C.); (J.W.L.)
| | - Johanna W. Lampe
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (L.L.); (K.R.C.); (J.W.L.)
- Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
| | - Meredith A.J. Hullar
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (L.L.); (K.R.C.); (J.W.L.)
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In Vitro Evaluation of Chemically Analyzed Hypericum Triquetrifolium Extract Efficacy in Apoptosis Induction and Cell Cycle Arrest of the HCT-116 Colon Cancer Cell Line. Molecules 2019; 24:molecules24224139. [PMID: 31731693 PMCID: PMC6891740 DOI: 10.3390/molecules24224139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 10/26/2019] [Accepted: 11/12/2019] [Indexed: 12/19/2022] Open
Abstract
Naturally derived drugs and plant-based products are attractive commodities that are being explored for cancer treatment. This in vitro study aimed to investigate the role of Hypericum triquetrifolium (50% ethanol: 50% water) extract (HTE) treatment on apoptosis, cell cycle modulation, and cell cycle arrest in human colon cancer cell line (HCT-116). HTE induced cell death via an apoptotic process, as assayed by an Annexin V-Cy3 assay. Exposing HCT-116 cells to 0.064, 0.125, 0.25, and 0.5 mg/mL of HTE for 24 h led to 50 ± 9%, 71.6 ± 8%, 85 ± 5%, and 96 ± 1.5% apoptotic cells, respectively. HCT-116 cells treated with 0.25 and 0.5 mg/mL HTE for 3 h resulted in 38.9 ± 1.5% and 57.2 ± 3% cleavage of caspase-3-specific substrate, respectively. RT-PCR analysis revealed that the HTE extract had no effect on mRNA levels of Apaf-1 and NOXA. Moreover, the addition of 0.125 mg/mL and 0.25 mg/mL HTE for 24 h was clearly shown to attenuate the cell cycle progression machinery in HCT-116 cells. GC/MS analysis of the extract identified 21 phytochemicals that are known as apoptosis inducers and cell cycle arrest agents. All the compounds detected are novel in H. triquetrifolium. These results suggest that HTE-induced apoptosis of human colon cells is mediated primarily through the caspase-dependent pathway. Thus, HTE appears to be a potent therapeutic agent for colon cancer treatment.
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Rodríguez-Miguel A, García-Rodríguez LA, Gil M, Barreira-Hernández D, Rodríguez-Martín S, de Abajo FJ. Population-based case-control study: chemoprotection of colorectal cancer with non-aspirin nonsteroidal anti-inflammatory drugs and other drugs for pain control. Aliment Pharmacol Ther 2019; 50:295-305. [PMID: 31313358 DOI: 10.1111/apt.15333] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 04/16/2019] [Accepted: 05/13/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Inflammation and overexpression of cyclooxygenase-2 (COX-2) have been described to play a key role in the progression from nonpathologic intestinal mucosa to colorectal cancer (CRC). AIMS To assess the chemoprotective effect of non-aspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) under different patterns of use in a Mediterranean population and to explore the potential effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs; chondroitin sulfate and glucosamine) and metamizole (or dipyrone), also reported to influence COX-2 activity. METHODS We performed a case-control study nested in a cohort extracted from the primary care database, BIFAP. From 2001 to 2014, we included 15 491 incident cases and 60 000 random controls. To estimate the association between the drugs of interest and CRC, we built logistic regression models to compute the adjusted-odds ratios (AOR) and 95% confidence intervals (CI). RESULTS NA-NSAIDs use was associated with a reduced risk of CRC (AOR = 0.67; 95% CI: 0.63-0.71) and increased linearly with duration of treatment (p for trend <0.001). The effect diminished upon discontinuation but persisted statistically significant up to 1 year. All individual NA-NSAIDs examined showed a decreased risk. The concomitant use of proton-pump inhibitors (PPI) had no impact on the protective effect of NA-NSAIDs; AORPPI + NSAID = 0.64; 0.58-0.71. SYSADOA use was associated with a reduced risk (0.79; 0.69-0.90) but disappeared after the exclusion of NSAID users during the previous 1 or 3 years (0.85; 0.70-1.04 and 1.00; 0.76-1.31 respectively). Metamizole did not show a chemoprotective effect. CONCLUSIONS NA-NSAID use is associated with a duration-dependent risk reduction of CRC not shared by SYSADOAs or metamizole.
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Affiliation(s)
- Antonio Rodríguez-Miguel
- Clinical Pharmacology Unit, University Hospital "Príncipe de Asturias", Madrid, Spain.,Department of Biomedical Sciences, Pharmacology Unit, School of Medicine, University of Alcalá (IRYCIS), Madrid, Spain
| | | | - Miguel Gil
- BIFAP Unit, Pharmacoepidemiology and Pharmacovigilance Division, Spanish Agency for Medicines and Clinical Devices (AEMPS), Madrid, Spain
| | - Diana Barreira-Hernández
- Clinical Pharmacology Unit, University Hospital "Príncipe de Asturias", Madrid, Spain.,Department of Biomedical Sciences, Pharmacology Unit, School of Medicine, University of Alcalá (IRYCIS), Madrid, Spain
| | - Sara Rodríguez-Martín
- Clinical Pharmacology Unit, University Hospital "Príncipe de Asturias", Madrid, Spain.,Department of Biomedical Sciences, Pharmacology Unit, School of Medicine, University of Alcalá (IRYCIS), Madrid, Spain
| | - Francisco J de Abajo
- Clinical Pharmacology Unit, University Hospital "Príncipe de Asturias", Madrid, Spain.,Department of Biomedical Sciences, Pharmacology Unit, School of Medicine, University of Alcalá (IRYCIS), Madrid, Spain
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Costea T, Hudiță A, Ciolac OA, Gălățeanu B, Ginghină O, Costache M, Ganea C, Mocanu MM. Chemoprevention of Colorectal Cancer by Dietary Compounds. Int J Mol Sci 2018; 19:E3787. [PMID: 30487390 PMCID: PMC6321468 DOI: 10.3390/ijms19123787] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 11/18/2018] [Accepted: 11/23/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds' bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.
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Affiliation(s)
- Teodora Costea
- Department of Pharmacognosy, Phytochemistry and Phytotherapy, "Carol Davila" University of Medicine and Pharmacy, 020956 Bucharest, Romania.
| | - Ariana Hudiță
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Oana-Alina Ciolac
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Bianca Gălățeanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Octav Ginghină
- Department of Surgery, "Sf. Ioan" Emergency Clinical Hospital, 042122 Bucharest, Romania.
- Department II, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, 030167 Bucharest, Romania.
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania.
| | - Constanța Ganea
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Maria-Magdalena Mocanu
- Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
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Glucosamine use and risk of colorectal cancer: results from the Cancer Prevention Study II Nutrition Cohort. Cancer Causes Control 2018; 29:389-397. [PMID: 29411204 DOI: 10.1007/s10552-018-1003-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 01/27/2018] [Indexed: 12/21/2022]
Abstract
PURPOSE Use of glucosamine supplements has been associated with reduced risk of colorectal cancer (CRC) in previous studies; however, information on this association remains limited. METHODS We examined the association between glucosamine use and CRC risk among 113,067 men and women in the Cancer Prevention Study II Nutrition Cohort. Glucosamine use was first reported in 2001 and updated every 2 years thereafter. Participants were followed from 2001 through June of 2011, during which time 1440 cases of CRC occurred. RESULTS As has been observed in prior studies, current use of glucosamine, modeled using a time-varying exposure, was associated with lower risk of CRC (HR 0.83; 95% CI 0.71-0.97) compared to never use. However, for reasons that are unclear, this reduction in risk was observed for shorter-duration use (HR 0.68; 95% CI 0.52-0.87 for current users with ≤ 2 years use) rather than longer-duration use (HR 0.90; 95% CI 0.72-1.13 for current users with 3 to < 6 years of use; HR 0.99; 95% CI 0.76-1.29 for current users with ≥ 6 years of use). CONCLUSIONS Further research is needed to better understand the association between glucosamine use and risk of CRC, and how this association may vary by duration of use.
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Possible role of chondroitin sulphate and glucosamine for primary prevention of colorectal cancer. Results from the MCC-Spain study. Sci Rep 2018; 8:2040. [PMID: 29391578 PMCID: PMC5794904 DOI: 10.1038/s41598-018-20349-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 01/10/2018] [Indexed: 12/21/2022] Open
Abstract
A safe and effective colorectal cancer (CRC) chemoprevention agent remains to be discovered. We aim to evaluate the association between the use of glucosamine and/or chondroitin sulphate and risk of colorectal cancer (CRC) in the MCC-Spain study, a case-control study performed in Spain that included 2140 cases of CRC and 3950 population controls. Subjects were interviewed on sociodemographic factors, lifestyle, family and medical history and regular drug use. Adjusted odds ratios and their 95% confidence intervals were estimated. The reported frequency of chondroitin and/or glucosamine use was 2.03% in controls and 0.89% in cases. Users had a reduced risk of CRC (OR: 0.47; 95% CI: 0.28–0.79), but it was no longer significant when adjusted for NSAID (nonsteroidal anti-inflammatory drugs) use (OR: 0.82; 95% CI: 0.47–1.40). A meta-analysis with previous studies suggested a protective effect, overall and stratified by NSAID use (OR: 0.77; 95% CI: 0.62–0.97). We have not found strong evidence of an independent preventive effect of CG on CRC in our population because the observed effects of our study could be attributed to NSAIDs concurrent use. These results merit further research due to the safety profile of these drugs.
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Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients 2017; 9:E290. [PMID: 28300758 PMCID: PMC5372953 DOI: 10.3390/nu9030290] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 02/22/2017] [Accepted: 03/13/2017] [Indexed: 12/20/2022] Open
Abstract
Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.
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Affiliation(s)
- Matthew Butawan
- Center for Nutraceutical and Dietary Supplement Research, School of Health Studies, The University of Memphis, Memphis, TN 38152, USA.
| | | | - Richard J Bloomer
- Center for Nutraceutical and Dietary Supplement Research, School of Health Studies, The University of Memphis, Memphis, TN 38152, USA.
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Hamishehkar H, Ranjdoost F, Asgharian P, Mahmoodpoor A, Sanaie S. Vitamins, Are They Safe? Adv Pharm Bull 2016; 6:467-477. [PMID: 28101454 DOI: 10.15171/apb.2016.061] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Revised: 10/09/2016] [Accepted: 10/15/2016] [Indexed: 12/14/2022] Open
Abstract
The consumption of a daily multivitamin among people all over the world is dramatically increasing in recent years. Most of the people believe that if vitamins are not effective, at least they are safe. However, the long term health consequences of vitamins consumption are unknown. This study aimed to assess the side effects and possible harmful and detrimental properties of vitamins and to discuss whether vitamins can be used as safe health products or dietary supplements. We performed a MEDLINE/PubMed, EMBASE, Scopus and Google Scholar search and assessed reference lists of the included studies which were published from 1993 through 2015. The studies, with an emphasis on RCTs (randomized controlled clinical trials), were reviewed. As some vitamins such as fat-soluble vitamins (vitamin A, vitamin D, vitamin E), and also some of the water-soluble vitamins like folic acid may cause adverse events and some like vitamin C is widely taken assuming that it has so many benefits and no harm, we included relevant studies with negative or undesired results regarding the effect of these vitamins on health. Our recommendation is that taking high-dose supplements of vitamins A, E, D, C, and folic acid is not always effective for prevention of disease, and it can even be harmful to the health.
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Affiliation(s)
- Hadi Hamishehkar
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farhad Ranjdoost
- Iranian Evidence Based Medicine Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parina Asgharian
- Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ata Mahmoodpoor
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sarvin Sanaie
- Tuberculosis & Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Yagdi E, Cerella C, Dicato M, Diederich M. Garlic-derived natural polysulfanes as hydrogen sulfide donors: Friend or foe? Food Chem Toxicol 2016; 95:219-33. [DOI: 10.1016/j.fct.2016.07.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 07/13/2016] [Accepted: 07/14/2016] [Indexed: 02/06/2023]
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Pohlig F, Ulrich J, Lenze U, Mühlhofer HML, Harrasser N, Suren C, Schauwecker J, Mayer-Kuckuk P, von Eisenhart-Rothe R. Glucosamine sulfate suppresses the expression of matrix metalloproteinase-3 in osteosarcoma cells in vitro. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:313. [PMID: 27562075 PMCID: PMC5000453 DOI: 10.1186/s12906-016-1315-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 08/23/2016] [Indexed: 01/02/2023]
Abstract
Background Glucosamine, a common dietary supplement, has a possible anti-sarcoma effect. However, an understanding of the underlying mechanism of such an effect is limited. For this study we hypothesized that glucosamine suppresses the basal level of matrix metalloproteinase expression in human osteosarcoma cell lines. Methods We examined the osteosarcoma cell lines, MG-63 and SaOS-2. Cells were exposed to 0, 10, 50 and 100 μg/ml glucosamine sulfate for 48 h and treatment toxicity was determined through measurement of cell viability and proliferation. Relative gene expression of matrix metalloproteinase (MMP)-2, -3 and -9 was quantified by real-time polymerase chain reaction. Protein levels of MMP-2 and -9 were assessed by ELISA. Results Administration of 10, 50 or 100 μg/ml glucosamine sulfate had no effect on the cell viability of MG-63 and SaOS-2 cells. A significant reduction of MMP expression in both cell lines was observed only for MMP-3, while a decrease in MMP-9 was seen in SaOS-2 cells. The expression of MMP-2 was not significantly affected in either cell line. Protein level of MMP-3 was reduced in both cell lines upon stimulation with 10 μg/ml glucosamine sulfate whereas for MMP-9 a decrease could only be observed in SaOS-2 cells. Conclusion In this study, we found a pronounced suppressive effect of glucosamine sulfate particularly on MMP-3 and also MMP-9 mRNA and protein levels in osteosarcoma cell lines in vitro. The data warrants further investigations into the potential anti-tumor efficacy of glucosamine sulfate in osteosarcoma. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1315-6) contains supplementary material, which is available to authorized users.
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Garavaglia J, Markoski MM, Oliveira A, Marcadenti A. Grape Seed Oil Compounds: Biological and Chemical Actions for Health. Nutr Metab Insights 2016; 9:59-64. [PMID: 27559299 PMCID: PMC4988453 DOI: 10.4137/nmi.s32910] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 07/20/2016] [Accepted: 07/22/2016] [Indexed: 12/30/2022] Open
Abstract
Grape seed oil is rich in phenolic compounds, fatty acids, and vitamins, with economic importance to pharmaceutical, cosmetic, and food industry. Its use as an edible oil has also been suggested, especially due to its pleasant sensory characteristics. Grape seed oil has beneficial properties for health that are mainly detected by in vitro studies, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, and may interact with cellular and molecular pathways. These effects have been related to grape seed oil constituents, mainly tocopherol, linolenic acid, resveratrol, quercetin, procyanidins, carotenoids, and phytosterols. The aim of this article was to briefly review the composition and nutritional aspects of grape seed oil, the interactions of its compounds with molecular and cellular pathways, and its possible beneficial effects on health.
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Affiliation(s)
- Juliano Garavaglia
- Institute of Technology in Food for Health, University of Vale do Rio dos Sinos (UNISINOS), São Leopoldo, Rio Grande do Sul, Brazil.; Department of Nutrition, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Melissa M Markoski
- Postgraduate Program in Health Sciences: Cardiology, Institute of Cardiology of Rio Grande do Sul (IC/FUC), Porto Alegre, Brazil.; Cellular and Molecular Cardiology Laboratory, Institute of Cardiology of Rio Grande do Sul (IC/FUC), Porto Alegre, Brazil
| | - Aline Oliveira
- Postgraduate Program in Health Sciences: Cardiology, Institute of Cardiology of Rio Grande do Sul (IC/FUC), Porto Alegre, Brazil
| | - Aline Marcadenti
- Department of Nutrition, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil.; Postgraduate Program in Health Sciences: Cardiology, Institute of Cardiology of Rio Grande do Sul (IC/FUC), Porto Alegre, Brazil
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Kantor ED, Zhang X, Wu K, Signorello LB, Chan AT, Fuchs CS, Giovannucci EL. Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study. Int J Cancer 2016; 139:1949-57. [PMID: 27357024 DOI: 10.1002/ijc.30250] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 06/15/2016] [Indexed: 12/14/2022]
Abstract
Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred. Cox proportional hazards regression was used to estimate relative risks (RRs) within each cohort, and results were pooled using a random effects meta-analysis. Associations were comparable across cohorts, with a RR of 0.79 (95% CI: 0.63-1.00) observed for any use of glucosamine and a RR of 0.77 (95% CI: 0.59-1.01) observed for any use of chondroitin. Use of glucosamine in the absence of chondroitin was not associated with risk of CRC, whereas use of glucosamine + chondroitin was significantly associated with risk (RR: 0.77; 95% CI: 0.58-0.999). The association between use of glucosamine + chondroitin and risk of CRC did not change markedly when accounting for change in exposure status over follow-up (RR: 0.75; 95% CI: 0.58-0.96), nor did the association significantly vary by sex, aspirin use, body mass index, or physical activity. The association was comparable for cancers of the colon and rectum. Results support a protective association between use of glucosamine and chondroitin and risk of CRC. Further study is needed to better understand the chemopreventive potential of these supplements.
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Affiliation(s)
- Elizabeth D Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Lisa B Signorello
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Andrew T Chan
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.,Division of Gastroenterology, Massachusetts General Hospital, Boston, MA.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA
| | - Charles S Fuchs
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
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38
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Myneni AA, Chang SC, Niu R, Liu L, Swanson MK, Li J, Su J, Giovino GA, Yu S, Zhang ZF, Mu L. Raw Garlic Consumption and Lung Cancer in a Chinese Population. Cancer Epidemiol Biomarkers Prev 2016; 25:624-33. [PMID: 26809277 PMCID: PMC4873399 DOI: 10.1158/1055-9965.epi-15-0760] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 12/11/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Evidence of anticancer properties of garlic for different cancer sites has been reported previously in in vitro and in vivo experimental studies but there is limited epidemiologic evidence on the association between garlic and lung cancer. METHODS We examined the association between raw garlic consumption and lung cancer in a case-control study conducted between 2005 and 2007 in Taiyuan, China. Epidemiologic data was collected by face-to-face interviews from 399 incident lung cancer cases and 466 healthy controls. We used unconditional logistic regression models to estimate crude and adjusted ORs (aOR) and their 95% confidence intervals (CI). Adjusted models controlled for age, sex, average annual household income 10 years ago, smoking, and indoor air pollution. RESULTS Compared with no intake, raw garlic intake was associated with lower risk of development of lung cancer with a dose-response pattern (aOR for <2 times/week = 0.56; 95% CI, 0.39-0.81 and aOR for ≥2 times/week = 0.50; 95% CI, 0.34-0.74; Ptrend = 0.0002). Exploratory analysis showed an additive interaction of raw garlic consumption with indoor air pollution and with any supplement use in association with lung cancer. CONCLUSIONS The results of the current study suggest that raw garlic consumption is associated with reduced risk of lung cancer in a Chinese population. IMPACT This study contributes to the limited research in human population on the association between garlic and lung cancer and advocates further investigation into the use of garlic in chemoprevention of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 624-33. ©2016 AACR.
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Affiliation(s)
- Ajay A Myneni
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, New York
| | - Shen-Chih Chang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California
| | - Rungui Niu
- Shanxi Tumor Hospital, Taiyuan, Shanxi Province, China
| | - Li Liu
- Taiyuan City Center for Disease Control and Prevention (CDC), Taiyuan, Shanxi Province, China
| | - Mya K Swanson
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, New York
| | - Jiawei Li
- School of Public Health, Fudan University, Shanghai, China
| | - Jia Su
- School of Public Health, Fudan University, Shanghai, China
| | - Gary A Giovino
- Department of Community Health and Health Behavior, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, New York
| | - Shunzhang Yu
- School of Public Health, Fudan University, Shanghai, China
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California
| | - Lina Mu
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York (SUNY) at Buffalo, Buffalo, New York.
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Norat T, Scoccianti C, Boutron-Ruault MC, Anderson A, Berrino F, Cecchini M, Espina C, Key T, Leitzmann M, Powers H, Wiseman M, Romieu I. European Code against Cancer 4th Edition: Diet and cancer. Cancer Epidemiol 2015; 39 Suppl 1:S56-66. [PMID: 26164653 DOI: 10.1016/j.canep.2014.12.016] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 12/19/2014] [Accepted: 12/30/2014] [Indexed: 12/11/2022]
Abstract
Lifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer. Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt.
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Affiliation(s)
- Teresa Norat
- Department of Epidemiology and Biostatistics, School of Public Health Imperial College London, St Mary's Campus, London W2 1PG, United Kingdom
| | - Chiara Scoccianti
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
| | | | - Annie Anderson
- Centre for Research into Cancer Prevention & Screening, Level 7, Mailbox 7, Ninewells Hospital & Medical School, Dundee DD1 9SY, Scotland, United Kingdom
| | - Franco Berrino
- Fondazione IRCSS Istituto Nazionale dei Tumori, 1 via Venezian, 20133 Milan, Italy
| | - Michele Cecchini
- Health Policy Analyst OECD, 2 rue André Pascal, 75775 Paris Cedex 16, France
| | - Carolina Espina
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
| | - Tim Key
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom
| | - Michael Leitzmann
- Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, 93042 Regensburg, Germany
| | - Hilary Powers
- Human Nutrition Unit, The Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom
| | - Martin Wiseman
- World Cancer Research Fund International, Second Floor, 22 Bedford Square, London WC1B 3HH, United Kingdom
| | - Isabelle Romieu
- International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
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Danilov AB, Grigorenko NV. [An antinociceptive effect of chondroprotectors: a myth or a reality?]. Zh Nevrol Psikhiatr Im S S Korsakova 2015; 115:84-89. [PMID: 26569010 DOI: 10.17116/jnevro20151159184-89] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Authors reviewed the literature on the efficacy of chondroprotectors in the treatment of chronic pain syndromes in comparison with placebo and other analgesics to discover the own antinociceptive effect of these drugs and mechanisms by which it occurs. Authors evaluated the results of various clinical studies on the effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) on chronic pain syndrome in osteoarthritis and low back pain. We compared their effects with those of NSAIDs, celecoxib, or placebo. Assessment of pain and functional status was performed using WOMAC, VASandLeken's index as well as the Roland--Morrisquality of life questionnaire. The review of a number of clinical studies revealed a definite antinociceptive and anti-inflammatory effect of SYSADOA comparable with NSAIDs not only in the treatment of osteoarthritis, but also in chronic back pain, which is characterized by early onset and gradual development with a long-term retention of the result even after discontinuation of therapy. It has been shown that SYSADOA are able to reduce the level of inflammatory cytokines in the blood (IL-6, C-reactive protein) and to activate the production of anti-inflammatory cytokine IL-10 in the synovial membrane. It is shown that blocking of the effects of interleukin 1-beta and thereby inhibition of inflammatory enzymes like nitric oxide synthase and cyclooxygenase-2 is one of the points of glucosamine chondrocytes application. The data obtained in numerous studies that confirm the ability of SYSADOA to inhibit proinflammatory cytokines open the new perspectives for their use in the treatment of not only joint pain but also other chronic pain syndromes.
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Affiliation(s)
- A B Danilov
- Sechenov First Moscow State Medical University, Moscow
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Jin X, Che DB, Zhang ZH, Yan HM, Jia ZY, Jia XB. Ginseng consumption and risk of cancer: A meta-analysis. J Ginseng Res 2015; 40:269-77. [PMID: 27616903 PMCID: PMC5005362 DOI: 10.1016/j.jgr.2015.08.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2015] [Revised: 08/23/2015] [Accepted: 08/25/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The findings of currently available studies are not consistent with regard to the association between the risk of cancer and ginseng consumption. Therefore, we aimed to evaluate this association by conducting a meta-analysis of different studies. METHODS To systematically evaluate the effect of ginseng consumption on cancer incidence, six databases were searched, including PubMed, Ovid Technologies, Embase, The Cochrane Library, China National Knowledge Infrastructure, and Chinese VIP Information, from 1990 to 2014. Statistical analyses based on the protocol employed for a systematic review were conducted to calculate the summary relative risks (RRs) and 95% confidence intervals (CIs). RESULTS We identified nine studies, including five cohort studies, three case-control studies, and one randomized controlled trial, evaluating the association between ginseng consumption and cancer risk; these studies involved 7,436 cases and 334,544 participants. The data from the meta-analysis indicated a significant 16% lower risk of developing cancer in patients who consumed ginseng (RR = 0.84, 95% CI = 0.76-0.92), with evidence of heterogeneity (p = 0.0007, I (2) = 70%). Stratified analyses suggested that the significant heterogeneity may result from the incidence data for gastric cancer that were included in this study. Publication bias also showed the same result as the stratified analyses. In addition, subgroup analyses for four specific types of cancer (colorectal cancer, lung cancer, gastric cancer, and liver cancer) were also performed. The summary RRs for ginseng intake versus no ginseng consumption were 0.77 for lung cancer, 0.83 for gastric cancer, 0.81 for liver cancer, and 0.77 for colorectal cancer. CONCLUSION The findings of this meta-analysis indicated that ginseng consumption is associated with a significantly decreased risk of cancer and that the effect is not organ specific.
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Affiliation(s)
- Xin Jin
- Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, Jiangsu, China
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, China
| | - Dao-biao Che
- Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, Jiangsu, China
| | - Zhen-hai Zhang
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong-mei Yan
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zeng-yong Jia
- Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, Jiangsu, China
- Corresponding author. The First Hospital of Suqian, 120 Suzhi Road, Suqian, Jiangsu 223800, China.
| | - Xiao-bin Jia
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, China
- Corresponding author. Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, People's Republic of China.
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Manna SK, Golla S, Golla JP, Tanaka N, Cai Y, Takahashi S, Krausz KW, Matsubara T, Korboukh I, Gonzalez FJ. St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling. Cancer Prev Res (Phila) 2015; 8:786-795. [PMID: 26069204 PMCID: PMC4584416 DOI: 10.1158/1940-6207.capr-14-0113] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Accepted: 05/28/2015] [Indexed: 12/13/2022]
Abstract
Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes.
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Affiliation(s)
- Soumen K Manna
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Srujana Golla
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Jaya Prakash Golla
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Naoki Tanaka
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Yan Cai
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Shogo Takahashi
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Kristopher W Krausz
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Tsutomu Matsubara
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | | | - Frank J Gonzalez
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
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Yao Q, Lin M, Wang Y, Lai Y, Hu J, Fu T, Wang L, Lin S, Chen L, Guo Y. Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK signaling pathways. Int J Mol Med 2015; 36:1118-26. [PMID: 26310655 DOI: 10.3892/ijmm.2015.2327] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Accepted: 08/10/2015] [Indexed: 11/05/2022] Open
Abstract
Curcumin has been found to exhibit anticancer activity and certain studies have shown that curcumin triggers the apoptosis of human A549 lung adenocarcinoma cells. However, the mechanism underlying curcumin‑mediated apoptosis is not completely understood. The present study was designed to investigate the effect of curcumin on the induction of apoptosis and apoptosis‑related factors in human A549 lung adenocarcinoma cells. Treatment of A549 cells with curcumin caused a concentration‑dependent inhibition of cell growth and an increase in apoptosis, as confirmed by THE MTT assay, flow cytometry and morphology analysis. Curcumin‑treatment of A549 cells induced a loss of the mitochondrial membrane potential and increased cytosolic cytochrome c. Furthermore, curcumin‑induced apoptosis was accompanied by changes in intracellular oxidative stress‑related enzymes, including decreased intracellular reactive oxygen species levels, increased superoxide dismutase and decreased malondialdehyde and 4‑hydroxynonenal. In addition, induction of apoptosis was also accompanied by phosphorylation and activation of mitogen‑activated protein kinase signaling pathway factors c‑Jun N‑terminal kinase, p38 and extracellular signal-regulated kinase.
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Affiliation(s)
- Qinghua Yao
- Key Laboratory of Traditional Chinese Medicine Oncology, Zhejiang Cancer Hospital, Banshan Qiao, Hangzhou, Zhejiang 310022, P.R. China
| | - Miao Lin
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Yuqi Wang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Yuebiao Lai
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Jingjing Hu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Ting Fu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Lu Wang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Shuyuan Lin
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Liangliang Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Yong Guo
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
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Garlic consumption and colorectal cancer risk in man: a systematic review and meta-analysis. Public Health Nutr 2015; 19:308-17. [PMID: 25945653 DOI: 10.1017/s1368980015001263] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Colorectal cancer shows large incidence variations worldwide that have been attributed to different dietary factors. We conducted a meta-analysis on the relationship between garlic consumption and colorectal cancer risk. DESIGN We systematically reviewed publications obtained by searching ISI Web of Knowledge, MEDLINE and EMBASE literature databases. We extracted the risk estimate of the highest and the lowest reported categories of intake from each study and conducted meta-analysis using a random-effects model. RESULTS The pooled analysis of all fourteen studies, seven cohort and seven case-control, indicated that garlic consumption was not associated with colorectal cancer risk (OR=0·93; 95 % CI 0·82, 1·06, P=0·281; I 2=83·6 %, P≤0·001). Separate analyses on the basis of cancer sites and sex also revealed no statistically significant effects on cancer risk. However, when separately analysed on the basis of study type, we found that garlic was associated with an approximately 37 % reduction in colorectal cancer risk in the case-control studies (combined risk estimate=0·63, 95 % CI 0·48, 0·82, P=0·001; I 2=75·6 %, P≤0·001). CONCLUSIONS Our results suggest that consumption of garlic is not associated with a reduced colorectal cancer risk. Further investigations are necessary to clarify the discrepancy between results obtained from different types of epidemiological studies.
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Luc L, Baumgart C, Weiss E, Georger L, Ambrosone CB, Zirpoli G, McCann SE. Dietary supplement use among participants of a databank and biorepository at a comprehensive cancer centre. Public Health Nutr 2015; 18:916-26. [PMID: 24866812 PMCID: PMC4443698 DOI: 10.1017/s1368980014001062] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 02/24/2014] [Accepted: 03/23/2014] [Indexed: 12/16/2022]
Abstract
OBJECTIVE We assessed the prevalence, patterns and predictors of dietary supplement use among participants of the databank and biorepository (DBBR) at a comprehensive cancer centre in western New York. DESIGN Archived epidemiological questionnaire data were obtained from the DBBR at Roswell Park Cancer Institute. Descriptive statistics and logistic regression explored the prevalence, patterns and predictors of lifetime use of four common supplements (multivitamins, vitamin C, vitamin E and calcium) and use of multivitamins, sixteen single vitamins/minerals and eighteen herbal/specialty supplements within the previous 10 years. SETTING Western New York, USA. SUBJECTS DBBR participants (n 8096) enrolled between December 2003 and July 2012 were included in these analyses: 66.9 % (n 5418) with cancer, 65.6 % (n 5309) women, mean age for patients v. cancer-free controls 59.9 (SD 12.6) years and 50.7 (SD 15.4) years, respectively. RESULTS Overall, 54.4 % of DBBR participants reported lifetime use of one or more supplements and 63.1 % reported use of one or more supplements within the previous 10 years (excluding multivitamins). Multivitamin use was high in this sample (lifetime: 64.1 %; 10 years: 71.3 %; current: 51.8 %). Supplementation was higher among cancer-free controls than cancer patients. Vitamin C, calcium and fish oil were the most common single vitamin, mineral and specialty product, respectively. CONCLUSIONS A consistently high and increasing proportion of dietary supplement use over time remains clear. Supplementation is prevalent among cancer patients and may even be higher than predicted in cancer-free individuals. Further studies should assess the safety and efficacy of specific supplements in reducing disease risk.
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Affiliation(s)
- LeQuyen Luc
- Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
- D’Youville College, Buffalo, NY, USA
| | | | | | | | - Christine B Ambrosone
- Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
| | - Gary Zirpoli
- Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
| | - Susan E McCann
- Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
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Navarro SL, White E, Kantor ED, Zhang Y, Rho J, Song X, Milne GL, Lampe PD, Lampe JW. Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans. PLoS One 2015; 10:e0117534. [PMID: 25719429 PMCID: PMC4342228 DOI: 10.1371/journal.pone.0117534] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 12/17/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans. METHODS We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin. RESULTS Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo. CONCLUSION Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer. TRIAL REGISTRATION ClinicalTrials.gov NCT01682694.
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Affiliation(s)
- Sandi L. Navarro
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
- * E-mail:
| | - Emily White
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Elizabeth D. Kantor
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
| | - Yuzheng Zhang
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Junghyun Rho
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Xiaoling Song
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Ginger L. Milne
- Division of Clinical Pharmacology, Vanderbilt University, School of Medicine, Nashville, Tennessee, United States of America
| | - Paul D. Lampe
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Johanna W. Lampe
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
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47
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Zhu B, Zou L, Qi L, Zhong R, Miao X. Allium vegetables and garlic supplements do not reduce risk of colorectal cancer, based on meta-analysis of prospective studies. Clin Gastroenterol Hepatol 2014; 12:1991-2001.e1-4; quiz e121. [PMID: 24681077 DOI: 10.1016/j.cgh.2014.03.019] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 03/14/2014] [Accepted: 03/14/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Laboratory studies have provided evidence that allium vegetables and garlic supplements might protect against colorectal cancer (CRC), but epidemiologic studies have produced inconsistent findings. METHODS We conducted a meta-analysis of prospective studies evaluating the associations between allium vegetables, garlic supplements, and CRC risk. We pooled effect measures using fixed- or random-effect models, assessing the highest vs the lowest intakes. We used a dose-response regression model to evaluate the relationship between allium vegetable intake and CRC risk. RESULTS Our analysis included 8 studies with 20 reports of the effects of allium vegetables (5458 patients with CRC including 7,125,067 person-years) and 5 studies with 11 reports of the effects of garlic supplements (2685 patients with CRC including 2,304,439 person-years). We found no association between higher intake of allium vegetables and CRC risk (relative risk [RR], 1.06; 95% confidence interval [CI], 0.96-1.17; P = .26). Intake of allium vegetables did not correspond to CRC risk (P for nonlinear = .24, P for linear = .20). In subgroup analysis, a higher consumption of allium vegetables was associated marginally with increased risk of colon cancer among women (RR, 1.23; 95% CI, 1.01-1.50; P = .05). Use of garlic supplements was associated significantly with an increased risk of CRC (RR, 1.18; 95% CI, 1.02-1.36; P = .03). CONCLUSIONS In a meta-analysis, we found no evidence that higher intake of allium vegetables reduced the risk for CRC. We observed that garlic supplements increased the risk for CRC, but this finding requires external validation.
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Affiliation(s)
- Beibei Zhu
- State Key Laboratory of Environment Health (Incubation), Ministry of Education Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Zou
- State Key Laboratory of Environment Health (Incubation), Ministry of Education Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lu Qi
- Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
| | - Rong Zhong
- State Key Laboratory of Environment Health (Incubation), Ministry of Education Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Xiaoping Miao
- State Key Laboratory of Environment Health (Incubation), Ministry of Education Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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48
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Heine-Bröring RC, Winkels RM, Renkema JMS, Kragt L, van Orten-Luiten ACB, Tigchelaar EF, Chan DSM, Norat T, Kampman E. Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies. Int J Cancer 2014; 136:2388-401. [PMID: 25335850 DOI: 10.1002/ijc.29277] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Accepted: 09/19/2014] [Indexed: 12/31/2022]
Abstract
Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta-analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up to January 2013. Original and peer-reviewed papers on dietary supplement use and colorectal cancer, colon cancer, or rectal cancer incidence were included. "Use-no use"(U-NU), "highest-lowest"(H-L) and "dose-response"(DR) meta-analyses were performed. Random-effects models were used to estimate summary estimates. In total, 24 papers were included in the meta-analyses. We observed inverse associations for colorectal cancer risk and multivitamin (U-NU: RR = 0.92; 95% CI: 0.87,0.97) and calcium supplements (U-NU: RR = 0.86; 95% CI: 0.79,0.95; H-L: RR = 0.80; 95% CI: 0.70,0.92; DR: for an increase of 100 mg/day, RR = 0.96; 95% CI: 0.94,0.99). Inconsistent associations were found for colon cancer risk and supplemental vitamin A and vitamin C, and for colorectal cancer risk and supplemental vitamin D, vitamin E, garlic and folic acid. Meta-analyses of observational studies suggest a beneficial role for multivitamins and calcium supplements on colorectal cancer risk, while the association with other supplements and colorectal cancer risk is inconsistent. Residual confounding of lifestyle factors might be present. Before recommendations can be made, an extensive assessment of dietary supplement use and a better understanding of underlying mechanisms is needed.
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Hu JY, Hu YW, Zhou JJ, Zhang MW, Li D, Zheng S. Consumption of garlic and risk of colorectal cancer: An updated meta-analysis of prospective studies. World J Gastroenterol 2014; 20:15413-15422. [PMID: 25386091 PMCID: PMC4223276 DOI: 10.3748/wjg.v20.i41.15413] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 05/17/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer.
METHODS: Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies.
RESULTS: A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59).
CONCLUSION: Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk.
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Kantor ED, Lampe JW, Navarro SL, Song X, Milne GL, White E. Associations between glucosamine and chondroitin supplement use and biomarkers of systemic inflammation. J Altern Complement Med 2014; 20:479-85. [PMID: 24738579 DOI: 10.1089/acm.2013.0323] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Glucosamine and chondroitin supplements have been shown to have anti-inflammatory properties in both in vitro studies and animal models; however, little is known about these relationships in humans. The VITamins and Lifestyle (VITAL) biomarker study evaluated the associations between use of these supplements and a panel of circulating inflammatory biomarkers. DESIGN Study participants included 217 men and women age 50-75 years living in the Seattle metropolitan area. Use of glucosamine and chondroitin supplements was ascertained by home interview/supplement inventory. Inflammation was assessed by using blood and urine collected at the time of home interview. Measures of systemic inflammation included plasma high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, soluble TNF receptors I and II, and urinary prostaglandin E2-metabolite (PGE-M). Multivariate-adjusted linear regression was used to evaluate the associations between supplement use and biomarkers of inflammation. RESULTS High users (14 or more pills/week) of chondroitin had 36% lower hsCRP (ratio, 0.64; 95% confidence interval [CI], 0.39-1.04; p for trend=.03) and 27% lower PGE-M (ratio, 0.73; 95% CI, 0.5-0.98; p for trend=.07) than nonusers. Compared with nonusers, high users of glucosamine had 28% lower hsCRP (ratio, 0.72; 95% CI, 0.47-1.08; p for trend=.09) and 24% lower PGE-M (ratio, 0.76; 95% CI, 0.59-0.97; p for trend=0.10). Use of glucosamine and chondroitin supplements was not associated with the other markers of inflammation. CONCLUSIONS These results support prior research suggesting that use of glucosamine and chondroitin is associated with reduced hsCRP and PGE2, but further work is needed to more definitively evaluate the anti-inflammatory potential of these supplements.
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Affiliation(s)
- Elizabeth D Kantor
- 1 Public Health Sciences Division, Fred Hutchinson Cancer Research Program , Seattle, WA
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