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Wu W, Mi Y, Meng Q, Li N, Li W, Wang P, Hou Y. Natural polyphenols as novel interventions for aging and age-related diseases: Exploring efficacy, mechanisms of action and implications for future research. CHINESE HERBAL MEDICINES 2024. [DOI: 10.1016/j.chmed.2024.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats. Nutrients 2022; 14:nu14142848. [PMID: 35889805 PMCID: PMC9323991 DOI: 10.3390/nu14142848] [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: 04/08/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 11/19/2022] Open
Abstract
Carvacrol is a dietary polyphenol from Lamiaceae plants that has been shown to possess a wide range of biological activities including antioxidant and antitumor effects. This study aimed to investigate its anti-inflammatory and antioxidant effects on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Forty-nine rats were randomly assigned to four treatment and three control groups. Over 60 days, MNNG (200 mg/kg BW) was orally applied to animals of groups 1–5 while the rats in groups 2–5 also received different doses of carvacrol (10, 25, 50, and 100 mg/kg BW, respectively) until the end of the experiment. Group 6 rats were treated with 100 mg/kg BW carvacrol and no MNNG whereas group 7 was the control group without any treatment. After the euthanasia of all rats, the inflammatory cytokines and oxidative stress parameters were assessed in the blood and tissues. The expression of caspase 9, Bax, and Bcl-2 proteins in the stomach tissues were investigated through histopathological examinations. Statistically significant differences were observed in the body weight, oxidative stress, and inflammation parameters of groups 1 to 6 compared to group 7 (p ≤ 0.001). Animals in MNNG groups 2 and 3 treated with the low dose carvacrol (10 and 25 mg/kg BW) showed significantly reduced oxidative stress, inflammation, and apoptotic effect compared to animals of the MNNG groups receiving increased doses of carvacrol (50 and 100 mg/kg BW) or no carvacrol. Rats exposed to MNNG exhibited gastric cancer cells in several areas. In the MNNG group receiving 100 mg/kg BW carvacrol, the inflammatory cell infiltration was observed in gastric mucosal and submucosal areas whereas MNNG rats supplemented with 10 and 25 mg/kg BW carvacrol showed no pathological alterations of the gastric cells. The results of this study indicate that significant antioxidant and anti-inflammatory effects induced by carvacrol at doses of 10 and 25 mg/kg BW interfered with gastric carcinogenesis induced by MNNG in Wistar rats as well as provide hepatoprotection. However, high doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis.
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Dang R, Wang M, Li X, Wang H, Liu L, Wu Q, Zhao J, Ji P, Zhong L, Licinio J, Xie P. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway. J Neuroinflammation 2022; 19:41. [PMID: 35130906 PMCID: PMC8822843 DOI: 10.1186/s12974-022-02400-6] [Citation(s) in RCA: 245] [Impact Index Per Article: 81.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 01/24/2022] [Indexed: 02/07/2023] Open
Abstract
Background The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. Methods A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)–EGFP infusion. Results The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. Conclusion These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-022-02400-6.
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Affiliation(s)
- Ruozhi Dang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.,Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Mingyang Wang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Xinhui Li
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.,Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Haiyang Wang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.,College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
| | - Lanxiang Liu
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.,Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China
| | - Qingyuan Wu
- Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, 404100, China
| | - Jianting Zhao
- Department of Neurology, Xinxiang Central Hospital, Xinxiang, 453000, China
| | - Ping Ji
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China.,Key Laboratory of Psychoseomadsy, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
| | - Lianmei Zhong
- Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Julio Licinio
- Department of Psychiatry and Behavioral Sciences, College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Peng Xie
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China. .,Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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Augimeri G, Montalto FI, Giordano C, Barone I, Lanzino M, Catalano S, Andò S, De Amicis F, Bonofiglio D. Nutraceuticals in the Mediterranean Diet: Potential Avenues for Breast Cancer Treatment. Nutrients 2021; 13:2557. [PMID: 34444715 PMCID: PMC8400469 DOI: 10.3390/nu13082557] [Citation(s) in RCA: 33] [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: 06/26/2021] [Revised: 07/22/2021] [Accepted: 07/25/2021] [Indexed: 12/12/2022] Open
Abstract
The traditional Mediterranean Diet constitutes a food model that refers to the dietary patterns of the population living in countries bordering the Mediterranean Sea in the early 1960s. A huge volume of literature data suggests that the Mediterranean-style diet provides several dietary compounds that have been reported to exert beneficial biological effects against a wide spectrum of chronic illnesses, such as cardiovascular and neurodegenerative diseases and cancer including breast carcinoma. Among bioactive nutrients identified as protective factors for breast cancer, natural polyphenols, retinoids, and polyunsaturated fatty acids (PUFAs) have been reported to possess antioxidant, anti-inflammatory, immunomodulatory and antitumoral properties. The multiple anticancer mechanisms involved include the modulation of molecular events and signaling pathways associated with cell survival, proliferation, differentiation, migration, angiogenesis, antioxidant enzymes and immune responses. This review summarizes the anticancer action of some polyphenols, like resveratrol and epigallocatechin 3-gallate, retinoids and omega-3 PUFAs by highlighting the important hallmarks of cancer in terms of (i) cell cycle growth arrest, (ii) apoptosis, (iii) inflammation and (iv) angiogenesis. The data collected from in vitro and in vivo studies strongly indicate that these natural compounds could be the prospective candidates for the future anticancer therapeutics in breast cancer disease.
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Affiliation(s)
- Giuseppina Augimeri
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
| | - Francesca Ida Montalto
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
| | - Cinzia Giordano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Ines Barone
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Marilena Lanzino
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Stefania Catalano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Sebastiano Andò
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Francesca De Amicis
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Daniela Bonofiglio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (G.A.); (F.I.M.); (C.G.); (I.B.); (M.L.); (S.C.); (S.A.); (F.D.A.)
- Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Italy
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Aarthy M, Panwar U, Singh SK. Structural dynamic studies on identification of EGCG analogues for the inhibition of Human Papillomavirus E7. Sci Rep 2020; 10:8661. [PMID: 32457393 PMCID: PMC7250877 DOI: 10.1038/s41598-020-65446-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 05/04/2020] [Indexed: 02/04/2023] Open
Abstract
High risk human papillomaviruses are highly associated with the cervical carcinoma and the other genital tumors. Development of cervical cancer passes through the multistep process initiated from benign cyst to increasingly severe premalignant dysplastic lesions in an epithelium. Replication of this virus occurs in the fatal differentiating epithelium and involves in the activation of cellular DNA replication proteins. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers constrains the cells into S-phase constructing an environment favorable for genome replication and cell proliferation. To date, no suitable drug molecules exist to treat HPV infection whereas anticipation of novel anti-HPV chemotherapies with distinctive mode of actions and identification of potential drugs are crucial to a greater extent. Hence, our present study focused on identification of compounds analogue to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems towards treatment of cancer. A three dimensional similarity search on the small molecule library from natural product database using EGCG identified 11 potential small molecules based on their structural similarity. The docking strategies were implemented with acquired small molecules and identification of the key interactions between protein and compounds were carried out through binding free energy calculations. The conformational changes between the apoprotein and complexes were analyzed through simulation performed thrice demonstrating the dynamical and structural effects of the protein induced by the compounds signifying the domination. The analysis of the conformational stability provoked us to describe the features of the best identified small molecules through electronic structure calculations. Overall, our study provides the basis for structural insights of the identified potential identified small molecules and EGCG. Hence, the identified analogue of EGCG can be potent inhibitors against the HPV 16 E7 oncoprotein.
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Affiliation(s)
- Murali Aarthy
- Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, 630004, India
| | - Umesh Panwar
- Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, 630004, India
| | - Sanjeev Kumar Singh
- Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, 630004, India.
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Almora-Pinedo Y, Arroyo-Acevedo J, Herrera-Calderon O, Chumpitaz-Cerrate V, Hañari-Quispe R, Tinco-Jayo A, Franco-Quino C, Figueroa-Salvador L. Preventive effect of Oenothera rosea on N-methyl-N-nitrosourea-(NMU) induced gastric cancer in rats. Clin Exp Gastroenterol 2017; 10:327-332. [PMID: 29270029 PMCID: PMC5729836 DOI: 10.2147/ceg.s142515] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Currently, gastric cancer (GC) is considered a public health problem worldwide. Using medicinal plants for the prevention of chronic diseases such as cancer constitutes new alternatives in traditional medicine. Oenothera rosea (OR) could be an option, but it needs to be evaluated. Aim The main objective of this study was to evaluate the protective effect of OR extract on N-methyl-N-nitrosourea (NMU)-induced GC in rats. Methods In total, 80 male Holtzman rats were randomized into five groups. Group A received the saline solution (5mL/kg), group B received NMU 500 μg/kg (cancer inductor) by oral administration for 16 weeks, and groups C, D, and E were treated with OR extract (100, 200, and 300 mg/kg, respectively) and NMU in order to evaluate the preventive effect on cancer induced by NMU for 16 weeks. Blood and histological samples of stomachs were collected to determine histopathological, biochemical, and hematological parameters between different experimental groups. Results Groups C, D, and E presented less histopathological changes such as anaplastic and hyperplastic cells, compared with group B. Hematological and biochemical parameters were recorded, and superoxide dismutase, malondialdehyde, and nitric oxide levels were statistically less than those of NMU group (P<0.05, P<0.01, and P<0.01). Conclusion Considering the histopathological signs and the antioxidant activity in vivo as well as hematological and biochemical parameters of ethanolic extract of OR, we concluded that its administration in rats has a protective effect on GC, which is induced experimentally. This species could be studied in clinical trials for patients with GC in the future.
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Affiliation(s)
| | - Jorge Arroyo-Acevedo
- Laboratory of Experimental Pharmacology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima
| | | | - Víctor Chumpitaz-Cerrate
- Laboratory of Physiology and Pharmacology, Faculty of Dentistry, Universidad Nacional Mayor de San Marcos, Lima
| | - Renán Hañari-Quispe
- Laboratory of Animal Physiology, Universidad Andina Néstor Cáceres Velasquez, Puno
| | - Aldo Tinco-Jayo
- Academic Department of Human Medicine, School of Pharmacy and Biochemistry, Universidad Nacional San Cristóbal de Huamanga, Ayacucho
| | - Cesar Franco-Quino
- Laboratory of Physiology and Pharmacology, Faculty of Dentistry, Universidad Nacional Mayor de San Marcos, Lima
| | - Linder Figueroa-Salvador
- School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
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Molecular aspects of cancer chemopreventive and therapeutic efficacies of tea and tea polyphenols. Nutrition 2017; 43-44:8-15. [DOI: 10.1016/j.nut.2017.06.006] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Revised: 05/29/2017] [Accepted: 06/20/2017] [Indexed: 12/21/2022]
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AL-Janabi AAHS, Tawfeeq EF. Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9. J Gastrointest Cancer 2016; 48:148-150. [DOI: 10.1007/s12029-016-9855-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Naito Y, Takagi T, Handa O, Yoshikawa T. Lipid hydroperoxide-derived modification of proteins in gastrointestinal tract. Subcell Biochem 2014; 77:137-148. [PMID: 24374925 DOI: 10.1007/978-94-007-7920-4_12] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Role of lipid peroxidation in the pathogenesis of gastrointestinal diseases has been evaluated by measuring the tissue levels of lipid peroxides as thiobarbituric acid-reactive substances in the animal models as well as human. Recently, N (ε)-(hexanoyl)lysine (HEL) and 4-hydroxy-2-nonenal (HNE) are recognized as reliable and sensitive biomarkers for the early phase and the late phase of lipid peroxidation, respectively. The presence of HNE- and HEL-modified proteins has been demonstrated in in vivo models of several gastrointestinal diseases. In the present review, we introduced HNE-modification of TRPV1 channel in esophageal epithelial cells, HEL-modification of tropomyosin 1 (TMP1) in gastric cancer cells, and HEL-modification of gastrokine 1 in the healing of gastric ulcer.
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Affiliation(s)
- Yuji Naito
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kamigyo-ku, Kyoto, 602-8566, Japan,
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Ma Y, Zhang L, Rong S, Qu H, Zhang Y, Chang D, Pan H, Wang W. Relation between gastric cancer and protein oxidation, DNA damage, and lipid peroxidation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:543760. [PMID: 24454985 PMCID: PMC3886607 DOI: 10.1155/2013/543760] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/29/2013] [Accepted: 12/01/2013] [Indexed: 12/19/2022]
Abstract
OBJECTS The aim of this study is to evaluate protein oxidation, DNA damage, and lipid peroxidation in patients with gastric cancer and to investigate the relationship between oxidative stress and gastric cancer. METHODS We investigated changes in serum protein carbonyl (PC), advanced oxidation protein products (AOPP), and 3-nitrotyrosine (3-NT) levels, as indicators of protein oxidation, serum 8-hydroxydeoxyguanosine (8-OHdG), as a biomarker of DNA damage, and malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), and 8-ISO-prostaglandin F2α (8-PGF) in serum, as lipid peroxidation markers in gastric cancer (GC) patients and healthy control. RESULTS Compared with control, a statistically significant higher values of 8-OHdG, PC, AOPP, and 3-NT were observed in the GC patients (P < 0.05). The products of lipid peroxidation, MDA, CD, 4-HNE, and 8-PGF, were significantly lower in the GC patients compared to those of control (P < 0.05). In addition, the products of oxidative stress were similar between the Helicobacter pylori positive and the negative subgroups of GC patients. CONCLUSIONS GC patients were characterized by increased protein oxidation and DNA damage, and decreased lipid peroxidation. Assessment of oxidative stress and augmentation of the antioxidant defense system may be important for the treatment and prevention of gastric carcinogenesis.
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Affiliation(s)
- Yongsheng Ma
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
| | - Lin Zhang
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
| | - Shengzhong Rong
- Public Health School, Mudanjiang Medical College, No. 3 Tongxiang Street, Aimin District, Mudanjiang, Heilongjiang 157011, China
| | - Hongyan Qu
- The Third Affiliated Hospital of Harbin Medical University, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Yannan Zhang
- Public Health School, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Dong Chang
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
| | - Hongzhi Pan
- Public Health School, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Wenbo Wang
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
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Fu JY, Gao J, Zhang ZY, Zheng JW, Luo JF, Zhong LP, Xiang YB. Tea consumption and the risk of oral cancer incidence: a case-control study from China. Oral Oncol 2013; 49:918-922. [PMID: 23731795 DOI: 10.1016/j.oraloncology.2013.05.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Revised: 05/01/2013] [Accepted: 05/06/2013] [Indexed: 11/17/2022]
Abstract
OBJECTIVES To evaluate the relation of tea consumption with the risk of oral cancer incidence. SUBJECTS AND METHODS A multicenter case-control study based on hospitalized population was conducted for evaluating the association of tea consumption with oral cancer risk in China. Black tea and green tea were separately analyzed. 723 cases and 857 controls were included. Unconditional multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of oral cancer for tea consumption. RESULTS The ORs for green tea consumption⩾8g/day compared with<4g/day were 0.72 (95% CI 0.54, 0.93) for men, and 0.93 (95% CI 0.74, 1.26) for women. The ORs for black tea consumption⩾6g/day compared with<2g/day were 0.97 (95% CI 0.74, 1.20) for men, and 0.91 (95% CI 0.68, 1.23) for women. Green tea intake was significantly associated with reduced risk of oral cancer in men, but not in women, and the association was stronger in heavily smoking men. There was no indication that black tea consumption was associated with decreased oral cancer risk. CONCLUSION The results of this study indicated that green tea consumption may decrease the risk of oral cancer in men especially for those smoking heavily.
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Affiliation(s)
- Jin-Ye Fu
- Department of Oral & Maxillofacial - Head & Neck Oncology, Ninth People's Hospital, School of Medicine, Jiao Tong University, Shanghai 200011, China.
| | - Jing Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai 200032, China
| | - Zhi-Yuan Zhang
- Department of Oral & Maxillofacial - Head & Neck Oncology, Ninth People's Hospital, School of Medicine, Jiao Tong University, Shanghai 200011, China.
| | - Jia-Wei Zheng
- Department of Oral & Maxillofacial - Head & Neck Oncology, Ninth People's Hospital, School of Medicine, Jiao Tong University, Shanghai 200011, China.
| | - Jian-Feng Luo
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200032, China
| | - Lai-Ping Zhong
- Department of Oral & Maxillofacial - Head & Neck Oncology, Ninth People's Hospital, School of Medicine, Jiao Tong University, Shanghai 200011, China
| | - Yong-Bing Xiang
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai 200032, China
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Nechuta S, Shu XO, Li HL, Yang G, Ji BT, Xiang YB, Cai H, Chow WH, Gao YT, Zheng W. Prospective cohort study of tea consumption and risk of digestive system cancers: results from the Shanghai Women's Health Study. Am J Clin Nutr 2012; 96:1056-63. [PMID: 23053557 PMCID: PMC3471195 DOI: 10.3945/ajcn.111.031419] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Data from in vitro and animal studies support a protective role for tea in the etiology of digestive system cancers; however, results from prospective cohort studies have been inconsistent. In addition, to our knowledge, no study has investigated the association of tea consumption with the incidence of all digestive system cancers in Chinese women. OBJECTIVE We investigated the association of regular tea intake (≥3 times/wk for >6 mo) with risk of digestive system cancers. DESIGN We used the Shanghai Women's Health Study, a population-based prospective cohort study of middle-aged and older Chinese women who were recruited in 1996-2000. Adjusted HRs and associated 95% CIs were derived from Cox regression models. RESULTS After a mean follow-up of 11 y, 1255 digestive system cancers occurred (stomach, esophagus, colorectal, liver, pancreas, and gallbladder/bile duct cancers) in 69,310 nonsmoking and non-alcohol-drinking women. In comparison with women who never drank tea, regular tea intake (mostly green tea) was associated with reduced risk of all digestive system cancers combined (HR: 0.86; 95% CI: 0.74, 0.98), and the reduction in risk increased as the amount and years of tea consumption increased (P-trend = 0.01 and P-trend < 0.01, respectively). For example, women who consumed ≥150 g tea/mo (∼2-3 cups/d) had a 21% reduced risk of digestive system cancers combined (HR: 0.79; 95% CI: 0.63, 0.99). The inverse association was found primarily for colorectal and stomach/esophageal cancers. CONCLUSION In this large prospective cohort study, tea consumption was associated with reduced risk of colorectal and stomach/esophageal cancers in Chinese women.
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Affiliation(s)
- Sarah Nechuta
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA
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Nagini S. Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 2012; 4:156-69. [PMID: 22844547 PMCID: PMC3406280 DOI: 10.4251/wjgo.v4.i7.156] [Citation(s) in RCA: 326] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2011] [Revised: 06/04/2012] [Accepted: 06/12/2012] [Indexed: 02/05/2023] Open
Abstract
Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitation and hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.
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Affiliation(s)
- Siddavaram Nagini
- Siddavaram Nagini, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
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Abstract
A Mediterranean diet appears to have health benefits in many domains of human health, mediated perhaps by its anti-inflammatory effects. Metabolism of fatty acids and subsequent eicosanoid production is a key mechanism by which a Mediterranean diet can exert anti-inflammatory effects. Both dietary fatty acids and fatty acid metabolism determine fatty acid availability for cyclooxygenase- and lipoxygenase-dependent production of eicosanoids, namely prostaglandins and leukotrienes. In dietary intervention studies and in observational studies of the Mediterranean diet, blood levels of fatty acids do reflect dietary intakes but are attenuated. Small differences in fatty acid levels, however, appear to be important, especially when exposures occur over long periods of time. This review summarizes how fat intakes from a Greek-style Mediterranean diet can be expected to affect fatty acid metabolizing proteins, with an emphasis on the metabolic pathways that lead to the formation of proinflammatory eicosanoids. The proteins involved in these pathways are ripe for investigation using proteomic approaches and may be targets for colon cancer prevention.
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Affiliation(s)
- Zora Djuric
- Department of Family Medicine, University of Michigan, Ann Arbor, Michigan 48109-5930, USA.
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15
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Okada H, Naito Y, Takagi T, Takaoka M, Oya-Ito T, Fukumoto K, Uchiyama K, Handa O, Kokura S, Nagano Y, Matsui H, Kato Y, Osawa T, Yoshikawa T. Detection of N-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells. J Clin Biochem Nutr 2011; 50:47-52. [PMID: 22247600 PMCID: PMC3246182 DOI: 10.3164/jcbn.11-39] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2011] [Accepted: 03/16/2011] [Indexed: 01/10/2023] Open
Abstract
Nε-(Hexanoyl)lysine, formed by the reaction of lysine with n-6 lipid hydroperoxide, is a lipid peroxidation marker during the initial stage of oxidative stress. The aim of the present study is to indentify Nε-(hexanoyl)lysine-modified proteins in neoplastic transformed gastric mucosal cells by N-methyl-N'-nitro-N-nitrosoguanidine, and to compare the levels of these proteins between gastric mucosal cells and normal gastric cells. Much greater fluorescence of 2-[6-(4'-hydroxy)phenoxyl-3H-xanthen-3-on-9-yl]benzoic acid, an index of the intracellular levels of reactive oxygen species, was observed for gastric mucosal cells compared to normal gastric cells. Nε-(Hexanoyl)lysine-modified proteins were detected by SDS-PAGE or two-dimensional electrophoresis and Western blotting using anti-Nε-(hexanoyl)lysine polyclonal antibody, and a protein band of between 30–40 kDa was clearly increased in gastric mucosal cells compared to normal gastric cells. Two Nε-(hexanoyl)lysine-modified protein spots in gastric mucosal cells were identified as the tropomyosin 1 protein by mass spectrometry using a MASCOT search. The existence of Nε-(hexanoyl)lysine modification in tropomyosin 1 was confirmed by Western blotting of SDS-PAGE-separated or two-dimensional electrophoresis-separated proteins as well as by the immunoprecipitation with anti-tropomyosin 1 antibody. These data indicate that Nε-(hexanoyl)lysine modification of tropomyosin 1 may be related to neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine in gastric epithelial cells.
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Affiliation(s)
- Hitomi Okada
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
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Yang CS, Wang H. Mechanistic issues concerning cancer prevention by tea catechins. Mol Nutr Food Res 2011; 55:819-31. [PMID: 21538856 DOI: 10.1002/mnfr.201100036] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Revised: 03/04/2011] [Accepted: 03/24/2011] [Indexed: 12/12/2022]
Abstract
The cancer preventive activities of tea (Camellia sinensis, Theaceae) have been demonstrated in animal models for cancers at different organ sites and suggested by some epidemiological studies. Many mechanisms for cancer prevention have been proposed based on studies in cell lines, which demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events may result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, it is not known whether these are the molecular mechanisms of inhibition of carcinogenesis in animals and humans. This article discusses the key issues involved in extrapolating results from cell line studies to mechanistic information in vivo and in translating animal studies to human cancer prevention.
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Affiliation(s)
- Chung S Yang
- Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
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17
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Cancer prevention by tea: Evidence from laboratory studies. Pharmacol Res 2011; 64:113-22. [PMID: 21397027 DOI: 10.1016/j.phrs.2011.03.001] [Citation(s) in RCA: 158] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2010] [Revised: 03/02/2011] [Accepted: 03/02/2011] [Indexed: 12/30/2022]
Abstract
The cancer preventive activities of tea (Camellia sinensis Theaceae) have been studied extensively. Inhibition of tumorigenesis by green tea extracts and tea polyphenols has been demonstrated in different animal models, including those for cancers of the skin, lung, oral cavity, esophagus, stomach, small intestine, colon, bladder, liver, pancreas, prostate, and mammary glands. Many studies in cell lines have demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events can result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, the molecular mechanisms of inhibition of carcinogenesis in animals and humans remain to be further investigated. Future research directions in this area are discussed.
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Intrinsic apoptosis and NF-κB signaling are potential molecular targets for chemoprevention by black tea polyphenols in HepG2 cells in vitro and in a rat hepatocarcinogenesis model in vivo. Food Chem Toxicol 2010; 48:3281-7. [DOI: 10.1016/j.fct.2010.09.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Revised: 07/31/2010] [Accepted: 09/01/2010] [Indexed: 01/02/2023]
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Zou C, Liu H, Feugang JM, Hao Z, Chow HHS, Garcia F. Green tea compound in chemoprevention of cervical cancer. Int J Gynecol Cancer 2010; 20:617-24. [PMID: 20686382 PMCID: PMC2918290 DOI: 10.1111/igc.0b013e3181c7ca5c] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVES Human papillomavirus (HPV) infection is closely associated with the development of more than 95% of cervical cancer. Clinical trials using several chemopreventive agents are underway, but results are inconclusive. Most agents used in trials inhibited the growth of cancer cells in vitro, and about half of patients had some degree of clinical responses; however, the therapeutic effect was confounded by high rates of spontaneous regression and relapse. The selection of nontoxic agents especially food, beverage, and natural products that suppress oncogenic HPV, inhibit malignant transformation, and can additionally be used long term may be important for cervical cancer prevention. METHODS We evaluated green tea compound (epigallocatechin gallate and polyphenols E) effects on immortalized cervical epithelial and cervical cancer cells. HPV-immortalized cervical epithelial cells, TCL1, and HPV-positive cervical cancer cells, Me180 and HeLa, were used in the study. The effects of green tea compounds on cell growth, apoptosis, cell cycle, and gene expression were examined and characterized. RESULTS Both epigallocatechin gallate and polyphenols E inhibited immortalized cervical epithelial and cancer cell growth. Apoptosis induction and cell cycle changes were observed in a dose-dependent manner. Western blot analysis of apoptosis-related proteins, p53 and p21, showed dose-dependent increase, whereas p27 was not affected. HPV-E7 protein expression was decreased by green tea compounds. CONCLUSIONS This study provides information on the potential mechanisms of action of green tea compounds in suppression of HPV-related cervical cells, and it will enable us to assess the feasibility of using these agents.
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Affiliation(s)
- Changping Zou
- Guangxi Medical University, Nanning City, China
- Arizona Cancer Center, The University of Arizona, Tuczon, AZ
| | | | - Jean M. Feugang
- Arizona Cancer Center, The University of Arizona, Tuczon, AZ
- Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS
| | - Zhengping Hao
- Arizona Cancer Center, The University of Arizona, Tuczon, AZ
| | - H-H Sherry Chow
- Arizona Cancer Center, The University of Arizona, Tuczon, AZ
| | - Francisco Garcia
- Arizona Cancer Center, The University of Arizona, Tuczon, AZ
- The University of Arizona National Center of Excellence in Women's Health, Tuczon, AZ
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Manikandan P, Murugan RS, Priyadarsini RV, Vinothini G, Nagini S. Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG. Life Sci 2010; 86:936-41. [PMID: 20434464 DOI: 10.1016/j.lfs.2010.04.010] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Revised: 04/15/2010] [Accepted: 04/21/2010] [Indexed: 12/12/2022]
Abstract
AIMS Combining apoptosis induction with anti-invasive and anti-angiogenic treatment is gaining increasing attention as a promising strategy for cancer chemoprevention. In the present study, eugenol (4-allyl-2-methoxyphenol) was evaluated for its chemopreventive effects on N-methyl-N(')-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in Wistar rats by analyzing markers of apoptosis, invasion and angiogenesis. MAIN METHODS The expressions of markers of apoptosis (Bcl-2, Bcl-xL, Bax, Apaf-1, cytochrome C, caspase-9, caspase-3 and poly(ADP-ribose)polymerase; PARP), invasion (matrix metalloproteinase-2; MMP-2, matrix metalloproteinase-9; MMP-9, reversion-inducing cysteine rich protein with Kazal motifs; RECK and tissue inhibitors of metalloproteinase-2; TIMP-2) and angiogenesis (vascular endothelial growth factor; VEGF and VEGF receptor1; VEGFR1) in stomach tissue of experimental and control animals were measured by gelatin zymogram, immunohistochemical, Western blot and RT-PCR analysis. KEY FINDINGS Rats administered MNNG developed gastric carcinomas that displayed apoptosis avoidance coupled to upregulation of pro-invasive and angiogenic factors. Administration of eugenol induced apoptosis via the mitochondrial pathway by modulating the Bcl-2 family proteins, Apaf-1, cytochrome C, and caspases and inhibiting invasion, and angiogenesis as evidenced by changes in the activities of MMPs and the expression of MMP-2 and -9, VEGF, VEGFR1, TIMP-2 and RECK. SIGNIFICANCE Phytochemicals such as eugenol that are capable of manipulating the equilibrium between pro- and anti-apoptotic proteins as well as the delicate balance between stimulators and inhibitors of invasion and angiogenesis are attractive candidates for preventing tumour progression.
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Affiliation(s)
- Palrasu Manikandan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
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Murugan RS, Uchida K, Hara Y, Nagini S. Black tea polyphenols modulate xenobiotic-metabolizing enzymes, oxidative stress and adduct formation in a rat hepatocarcinogenesis model. Free Radic Res 2009; 42:873-84. [DOI: 10.1080/10715760802506331] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer 2009; 9:429-39. [PMID: 19472429 PMCID: PMC2829848 DOI: 10.1038/nrc2641] [Citation(s) in RCA: 820] [Impact Index Per Article: 51.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Extracts of tea, especially green tea, and tea polyphenols have been shown to inhibit the formation and development of tumours at different organ sites in animal models. There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate, inhibit enzyme activities and signal transduction pathways, resulting in the suppression of cell proliferation and enhancement of apoptosis, as well as the inhibition of cell invasion,angiogenesis and metastasis. Here, we review these biological activities and existing data relating tea consumption to human cancer risk in an attempt to understand the potential use of tea for cancer prevention.
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Affiliation(s)
- Chung S Yang
- Susan Lehman Cullman Laboratory of Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
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Letchoumy PV, Mohan KVPC, Prathiba D, Hara Y, Nagini S. Comparative evaluation of antiproliferative, antiangiogenic and apoptosis inducing potential of black tea polyphenols in the hamster buccal pouch carcinogenesis model. J Carcinog 2007; 6:19. [PMID: 18053169 PMCID: PMC2217513 DOI: 10.1186/1477-3163-6-19] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2007] [Accepted: 12/03/2007] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND To evaluate the relative chemopreventive efficacy of two black tea polyphenols, Polyphenon-B [P-B] and BTF-35 on 7,12-dimethylbenz [a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. METHODS Hamsters were divided into 6 groups. The right buccal pouches of animals in groups 1-3 were painted with 0.5% of DMBA three times a week for 14 weeks. While hamsters in group 1 received no further treatment, animals in groups 2 and 3 received diet containing 0.05% P-B and BTF-35 respectively, four weeks before DMBA painting that was continued until the end of the experiments. Animals in groups 4 and 5 were given P-B and BTF-35 alone respectively as in groups 2 and 3. Group 6 animals served as the untreated control. All the animals were sacrificed after 18 weeks. The expression of p21, cyclin D1, glutathione S-transferase pi (GST-P), nuclear factor kappa B (NF-kappaB), Bcl-2, Bax, cytochrome C, caspase-3, caspase-9, poly(ADP-ribose) polymerase (PARP), cytokeratins and vascular endothelial growth factor (VEGF) was analysed by RT-PCR, immunohistochemical and Western blot analyses. RESULTS DMBA treated animals developed buccal pouch carcinomas that displayed increased expression of p21, cyclin D1, GST-P, NF-kappaB, cytokeratins, VEGF and Bcl-2 with decreased expression of Bax, cytochrome C, caspase-3, caspase-9, and PARP. Dietary administration of both P-B and BTF-35 reduced the incidence of DMBA-induced HBP carcinomas by modulating markers of cell proliferation, cell survival, tumour infiltration, angiogenesis, and apoptosis. CONCLUSION The results of the present study provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. The greater efficacy of BTF-35 in inhibiting HBP carcinogenesis and modulating multiple molecular targets may have a potential role in the prevention of oral cancer.
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Affiliation(s)
- Paramasivame Vidjaya Letchoumy
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
| | | | - Duvuru Prathiba
- Department of Pathology, Sri Ramachandra Medical College and Research Institute, Chennai-600 116, Tamil Nadu, India
| | | | - Siddavaram Nagini
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
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