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Adami GR, Tangney C, Schwartz JL, Dang KC. Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans. Molecules 2020; 25:molecules25204753. [PMID: 33081212 PMCID: PMC7594096 DOI: 10.3390/molecules25204753] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/09/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023] Open
Abstract
Consumption of green tea (GT) and GT polyphenols has prevented a range of cancers in rodents but has had mixed results in humans. Human subjects who drank GT for weeks showed changes in oral microbiome. However, GT-induced changes in RNA in oral epithelium were subject-specific, suggesting GT-induced changes of the oral epithelium occurred but differed across individuals. In contrast, studies in rodents consuming GT polyphenols revealed obvious changes in epithelial gene expression. GT polyphenols are poorly absorbed by digestive tract epithelium. Their metabolism by gut/oral microbial enzymes occurs and can alter absorption and function of these molecules and thus their bioactivity. This might explain the overall lack of consistency in oral epithelium RNA expression changes seen in human subjects who consumed GT. Each human has different gut/oral microbiomes, so they may have different levels of polyphenol-metabolizing bacteria. We speculate the similar gut/oral microbiomes in, for example, mice housed together are responsible for the minimal variance observed in tissue GT responses within a study. The consistency of the tissue response to GT within a rodent study eases the selection of a dose level that affects tumor rates. This leads to the theory that determination of optimal GT doses in a human requires knowledge about the gut/oral microbiome in that human.
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Affiliation(s)
- Guy R. Adami
- Department of Oral Medicine & Diagnostic Sciences, Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 South Paulina Street, Chicago, IL 60612, USA; (J.L.S.); (K.C.D.)
- Correspondence: ; Tel.: +1-312-996-6251
| | - Christy Tangney
- Department of Clinical Nutrition, College of Health Sciences, Rush University Medical Center, 600 South Paulina St, Room 716 AAC, Chicago, IL 60612, USA;
| | - Joel L. Schwartz
- Department of Oral Medicine & Diagnostic Sciences, Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 South Paulina Street, Chicago, IL 60612, USA; (J.L.S.); (K.C.D.)
| | - Kim Chi Dang
- Department of Oral Medicine & Diagnostic Sciences, Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 South Paulina Street, Chicago, IL 60612, USA; (J.L.S.); (K.C.D.)
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Wang LX, Shi YL, Zhang LJ, Wang KR, Xiang LP, Cai ZY, Lu JL, Ye JH, Liang YR, Zheng XQ. Inhibitory Effects of (-)-Epigallocatechin-3-gallate on Esophageal Cancer. Molecules 2019; 24:molecules24050954. [PMID: 30857144 PMCID: PMC6429180 DOI: 10.3390/molecules24050954] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 02/24/2019] [Accepted: 03/04/2019] [Indexed: 02/06/2023] Open
Abstract
There is epidemiological evidence showing that drinking green tea can lower the risk of esophageal cancer (EC). The effect is mainly attributed to tea polyphenols and their most abundant component, (−)-epigallocatechin-3-gallate (EGCG). The possible mechanisms of tumorigenesis inhibition of EGCG include its suppressive effects on cancer cell proliferation, angiogenesis, DNA methylation, metastasis and oxidant stress. EGCG modulates multiple signal transduction and metabolic signaling pathways involving in EC. A synergistic effect was also observed when EGCG was used in combination with other treatment methods.
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Affiliation(s)
- Liu-Xiang Wang
- China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Zhengzhou 450008, Henan, China.
| | - Yun-Long Shi
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Long-Jie Zhang
- Ningbo Huangjinyun Tea Science and Technology Co. Ltd., Yuyao 315412, China.
| | - Kai-Rong Wang
- Ningbo Huangjinyun Tea Science and Technology Co. Ltd., Yuyao 315412, China.
| | - Li-Ping Xiang
- National Tea and Tea Product Quality Supervision and Inspection Center (Guizhou), Zunyi 563100, China.
| | - Zhuo-Yu Cai
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Jian-Liang Lu
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Jian-Hui Ye
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Yue-Rong Liang
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Xin-Qiang Zheng
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
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Shubin AV, Lesovaya EA, Kirsanov KI, Antoshina EE, Trukhanova LS, Gorkova TG, Belitsky GA, Yakubovskaya MG, Demidyuk IV. Re-Examination of the Esophageal Squamous Cell Carcinoma Model in Rats Induced by N-Nitrososarcosine Ethyl Ester Precursors. Bull Exp Biol Med 2018; 164:676-679. [PMID: 29577190 DOI: 10.1007/s10517-018-4057-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Indexed: 11/27/2022]
Abstract
Studies of the molecular mechanisms of esophageal cancer development have to be carried out on sufficient amount of tumor material, obtained under conditions of controlled exposure to carcinogenic factors. Esophageal cancer models on laboratory animals serve an indispensable source of this material. One of these models is esophageal cancer induction in rats by N-nitroso compound precursors. Despite adequate reproduction of human esophageal cancer, this model in fact has not been used since the 1990ies. Re-examination of esophageal cancer model, induced by N-nitrososarcosine ethyl ester precursors, is carried out and its efficiency in induction of squamous cell carcinoma is confirmed.
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Affiliation(s)
- A V Shubin
- Institute of Molecular Genetics, the Russian Academy of Sciences, Moscow, Russia
| | - E A Lesovaya
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - K I Kirsanov
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - E E Antoshina
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - L S Trukhanova
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - T G Gorkova
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - G A Belitsky
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - M G Yakubovskaya
- N. N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russia
| | - I V Demidyuk
- Institute of Molecular Genetics, the Russian Academy of Sciences, Moscow, Russia.
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Chen Y, Tong Y, Yang C, Gan Y, Sun H, Bi H, Cao S, Yin X, Lu Z. Consumption of hot beverages and foods and the risk of esophageal cancer: a meta-analysis of observational studies. BMC Cancer 2015; 15:449. [PMID: 26031666 PMCID: PMC4457273 DOI: 10.1186/s12885-015-1185-1] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 03/12/2015] [Indexed: 12/30/2022] Open
Abstract
Background Previous studies have mostly focused on the effects of specific constituents of beverages and foods on the risk of esophageal cancer (EC). An increasing number of studies are now emerging examining the health consequences of the high temperature of beverages and foods. We conducted a meta-analysis to summarize the evidence and clarify the association between hot beverages and foods consumption and EC risk. Methods We searched the PubMed, Embase, and Web of Science databases for relevant studies, published before May 1, 2014, with the aim to estimate the association between hot beverage and food consumption and EC risk. A random-effect model was used to pool the results from the included studies. Publication bias was assessed by using the Begg test, the Egger test, and funnel plot. Results Thirty-nine studies satisfied the inclusion criteria, giving a total of 42,475 non-overlapping participants and 13,811 EC cases. Hot beverage and food consumption was significantly associated with EC risk, with an odds ratio (OR) of 1.82 (95% confidence interval [CI], 1.53–2.17). The risk was higher for esophageal squamous cell carcinoma, with a pooled OR of 1.60 (95% CI, 1.29–2.00), and was insignificant for esophageal adenocarcinoma (OR: 0.79; 95% CI: 0.53–1.16). Subgroup analyses suggests that the association between hot beverage and food consumption and EC risk were significant in Asian population (OR: 2.06; 95% CI: 1.62-2.61) and South American population (OR: 1.52; 95% CI: 1.25-1.85), but not significant in European population (OR: 0.95; 95% CI: 0.68-1.34). Conclusions Hot beverage and food consumption is associated with a significantly increased risk of EC, especially in Asian and South American populations, indicating the importance in changing people’s dietary habits to prevent EC.
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Affiliation(s)
- Yawen Chen
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Yeqing Tong
- Center for Disease Control and Prevention of Hubei Province, Wuhan, Hubei, China.
| | - Chen Yang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Yong Gan
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Huilian Sun
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Huashan Bi
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Shiyi Cao
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Xiaoxv Yin
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Zuxun Lu
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem 2014; 5:355-376. [PMID: 25225603 PMCID: PMC4160529 DOI: 10.4331/wjbc.v5.i3.355] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
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Thakur J, Gupta R. Improvement of tea leaves fermentation through pectinases. Acta Microbiol Immunol Hung 2012; 59:321-34. [PMID: 22982636 DOI: 10.1556/amicr.59.2012.3.3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The pectinase enzymes isolated from Aspergillus niger, Byssochlamys fulva and Mucor circinelloides were used for fermentation of tea leaves from Camellia sinensis plant. The use of partially purified enzymes from Aspergillus niger and Mucor circinelloides resulted in significant (p < 0.001) increase in the phenolic compounds, hence, improvement in tea quality. Maximum increase in phenolic compounds was found in tea leaves treated with partially purified polygalacturonase (PGase) from Mucor circinelloides. Hence, purified polygalacturonase from Mucor circinelloides was used to study its effect on the improvement of tea leaves fermentation. The partially purified polygalacturonase from Mucor circinelloides was found to be most effective in tea fermentation, whereas pectin lyase from Byssochlamys fulva had little role in improvement of tea quality.
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Affiliation(s)
- Jagriti Thakur
- 1 Himachal Pradesh University Deparment of Biotechnology Summer Hill Shimla 171005 India
| | - Reena Gupta
- 1 Himachal Pradesh University Deparment of Biotechnology Summer Hill Shimla 171005 India
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Sissing L, Marnewick J, de Kock M, Swanevelder S, Joubert E, Gelderblom W. Modulating effects of rooibos and honeybush herbal teas on the development of esophageal papillomas in rats. Nutr Cancer 2011; 63:600-10. [PMID: 21541901 DOI: 10.1080/01635581.2011.539313] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Widespread consumption of herbal teas has stimulated interest in their role as cancer preventive agents. The present investigation monitored the modulation of methylbenzylnitrosamine (MBN)-induced esophageal squamous cell carcinogenesis by rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal and Camellia sinensis teas in male F344 rats. The tumor multiplicity was significantly (P < 0.05) inhibited by unfermented honeybush (45.5%), green (50%), and black (36%) teas, while the other teas exhibited weaker effects (<30% inhibition). The mean total papilloma size was reduced by unfermented rooibos (87%), unfermented honeybush (94%), and fermented honeybush (74%) due to the absence of large papillomas (>10 mm(3)). Reduction of the mean total papilloma number correlated with the total polyphenol (TPP) (r = 0.79; P < 0.02) and flavanol/proanthocyanidin (FLAVA) (r = 0.89; P < 0.008) intake (mg/100 g body weight) of the teas and the FLAVA (r = 0.89; P < 0.04) and flavonol/flavones/xanthones (r = 0.99; P < 0.002) intake when considering only the herbal teas. A daily TPP intake threshold of 7 mg/100 g body weight existed below where no inhibition of papilloma development was observed. Fermentation of herbal teas reduced the inhibitory effects on papilloma development associated with a reduction in the polyphenolic constituents. The inhibitory effect of herbal teas on papilloma development is associated with different flavonoid subgroups and/or combination thereof.
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Affiliation(s)
- Linda Sissing
- PROMEC Unit, Medical Research Council, Tygerberg, South Africa
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8
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Yuan JM. Green tea and prevention of esophageal and lung cancers. Mol Nutr Food Res 2011; 55:886-904. [PMID: 21538848 DOI: 10.1002/mnfr.201000637] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Revised: 03/14/2011] [Accepted: 03/30/2011] [Indexed: 02/06/2023]
Abstract
Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also have shown to suppress cell proliferation and induce apoptosis. Besides antioxidative property, green tea polyphenols have pro-oxidative activities under certain conditions and modulate phase II metabolic enzymes that can enhance the detoxification pathway of environmental toxicants and carcinogens. Although epidemiological studies have provided inconclusive results on the effect of green tea consumption against the development of esophageal and lung cancers in humans overall, the inverse association between green tea intake and risk of esophageal cancer risk is more consistently observed in studies with adequate control for potential confounders. Epidemiological studies also have demonstrated an inverse, albeit moderate, association between green tea consumption and lung cancer, especially in non-smokers. This article reviews data on the cancer-preventive activities of green tea extract and green tea polyphenols and possible mechanisms against the esophageal and lung carcinogenesis in experimental animals, and summarizes the current knowledge from epidemiological studies on the relationship between green tea consumption and esophageal and lung cancer risk in humans.
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Affiliation(s)
- Jian-Min Yuan
- University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
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Krishnan R, Raghunathan R, Maru GB. Effect of polymeric black tea polyphenols on benzo(a)pyrene [B(a)P]-induced cytochrome P4501A1 and 1A2 in mice. Xenobiotica 2008; 35:671-82. [PMID: 16316927 DOI: 10.1080/00498250500202155] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The chemopreventive activity of green tea polyphenols (GTPs) is, in part, due to modulation of cytochrome P450s (CYPs). To investigate the enzyme modulatory properties of major black tea polyphenols, the effect of decaffeinated black tea extract (DBTE) or polymeric black tea polyphenol (PBP) mix was studied on CYP1A1 and CYP1A2 in mouse tissues. Animals receiving 2.5% DBTE or 1% PBP mix or drinking water (15 days) were challenged with single oral benzo(a)pyrene (B(a)P) (1 mg/mouse) treatment on the 14th day. Liver and lung microsomes isolated after 24 h were analysed for CYP1A1 and CYP1A2, using biochemical substrate(s) and Western blot analysis. Treatment with 2.5% DBTE or 1% PBP mix did not significantly alter the basal activity and level of CYP1A1 and CYP1A2, whereas pretreatment with 2.5% DBTE or 1% PBP mix resulted in a significant decrease in both the activity and the level of B(a)P-induced CYP1A1 and CYP1A2 in liver and lungs. The PBP mix possesses enzyme modulatory properties exhibited by monomeric GTPs.
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Affiliation(s)
- R Krishnan
- Tobacco Carcinogenesis Group, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
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Stoner GD, Wang LS, Chen T. Chemoprevention of esophageal squamous cell carcinoma. Toxicol Appl Pharmacol 2007; 224:337-49. [PMID: 17475300 PMCID: PMC2128258 DOI: 10.1016/j.taap.2007.01.030] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2006] [Revised: 01/19/2007] [Accepted: 01/26/2007] [Indexed: 12/12/2022]
Abstract
Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.
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Affiliation(s)
- Gary D Stoner
- Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210, USA.
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Shammas MA, Neri P, Koley H, Batchu RB, Bertheau RC, Munshi V, Prabhala R, Fulciniti M, Tai YT, Treon SP, Goyal RK, Anderson KC, Munshi NC. Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. Blood 2006; 108:2804-10. [PMID: 16809610 PMCID: PMC1895573 DOI: 10.1182/blood-2006-05-022814] [Citation(s) in RCA: 128] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation.
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Affiliation(s)
- Masood A Shammas
- Veterans Administration Boston Health Care System, and Dana Farber Cancer Institute/Harvard Medical School, 44 Binney Street, D1B25, Boston, MA 02115, USA
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Chandra Mohan KVP, Hara Y, Abraham SK, Nagini S. Comparative evaluation of the chemopreventive efficacy of green and black tea polyphenols in the hamster buccal pouch carcinogenesis model. Clin Biochem 2006; 38:879-86. [PMID: 16098960 DOI: 10.1016/j.clinbiochem.2005.06.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2005] [Revised: 06/06/2005] [Accepted: 06/28/2005] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To evaluate the comparative chemopreventive efficacy of green tea polyphenols (Polyphenon-E) and black tea polyphenols (Polyphenon-B) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. DESIGN AND METHODS Hamsters were divided into 6 groups. Animals in group 1 served as controls. Animals in groups 2 and 3 were administered 0.05% Polyphenon-E and B, respectively, in the diet. The right buccal pouches of animals in groups 4-6 were painted with 0.5% DMBA three times a week for 14 weeks. While group 4 received no further treatment, hamsters in groups 5 and 6 received diet containing 0.05% Polyphenon-E and B, respectively. The status of carcinogen-metabolising enzymes, lipid peroxidation and glutathione-dependent antioxidants in the buccal pouch and liver, as well as the frequency of bone marrow micronuclei were used as biomarkers. RESULTS Application of DMBA induced HBP carcinomas, increased genotoxicity with an imbalance in carcinogen-metabolising enzymes and the cellular redox status. Inhibition of HBP carcinomas by Polyphenon-E and B was associated with a significant decrease in phase I enzymes, modulation of lipid peroxidation and enhanced antioxidant and phase II enzyme activities. CONCLUSION The greater efficacy of Polyphenon-B in inhibiting HBP carcinogenesis suggests that it may have a major impact in the chemoprevention of oral cancer.
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Affiliation(s)
- K V P Chandra Mohan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
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Abstract
AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis.
METHODS: HepG2 cells were seeded at a density of 5×105/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21WAF1 proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells.
RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21WAF1 protein and downregulation of Bcl-2 protein.
CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.
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Affiliation(s)
- Xu-Dong Jia
- Institute for Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing 100050 China.
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Elmore E, Siddiqui S, Navidi M, Steele VE, Redpath JL. Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels. J Cell Biochem 2005; 95:571-88. [PMID: 15786488 DOI: 10.1002/jcb.20426] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The human epidermal cell (HEC) assay, which uses carcinogen exposed normal skin keratinocytes to screen for cancer prevention efficacy, was used to screen possible preventive agents. The endpoints measured were inhibition of carcinogen-induced growth and induction of involucrin, an early marker of differentiation. Sixteen of twenty agents (apigenin, apomine, budesonide, N-(2-carboxyphenyl)retinamide, ellagic acid, ibuprofen, indomethacin, melatonin, (-)-2-oxo-4-thiazolidine carboxylic acid, polyphenon E, resveratrol, beta-sitosterol, sulfasalazine, vitamin E acetate, and zileuton) were positive in at least one of the two assay endpoints. Four agents (4-methoxyphenol, naringenin, palmitoylcarnitine chloride, and silymarin) were negative in the assay. Nine of the sixteen agents were positive for both endpoints. Agents that showed the greatest response included: ellagic acid > budesonide, ibuprofen > apigenin, and quinicrine dihydrochloride. Fifty-eight of sixty-five agents that have been evaluated in the HEC assay have also been evaluated in one or more rodent bioassays for cancer prevention and several are in clinical trials for cancer prevention. The assay has an overall predictive accuracy of approximately 91.4% for efficacy in rodent cancer prevention irrespective of the species used, the tissue model, or the carcinogen used. Comparison of the efficacious concentrations in vitro to plasma levels in clinical trials show that concentrations that produced efficacy in the HEC assay were achieved in clinical studies for 31 of 33 agents for which plasma levels and/or C(max) levels were available. For two agents, 9-cis-retinoic acid (RA) and dehydroepiandrosterone (DHEA), the plasma levels greatly exceeded the highest concentration (HC) found to have efficacy in vitro. Thus, the HEC assay has an excellent predictive potential for animal efficacy and is responsive at clinically achievable concentrations.
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Affiliation(s)
- Eugene Elmore
- Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697, USA.
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16
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de Boer JG, Yang H, Holcroft J, Skov K. Chemoprotection Against N-Nitrosomethylbenzylamine-Induced Mutation in the Rat Esophagus. Nutr Cancer 2004; 50:168-73. [PMID: 15623463 DOI: 10.1207/s15327914nc5002_6] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Prevention of esophageal cancer may be possible through dietary modification or supplementation. In this study we have investigated the mutation preventive properties of ellagic acid, green tea, and diallyl sulfide (DAS) against the mutagenicity of the nitrosamine N-nitrosomethylbenzylamine (NMBA) in the esophagus of the rat. In addition, the effect of the consumption of ethanol on the mutagenicity of NMBA was examined. NMBA is specific in inducing tumors in the rat esophagus and has been used in many studies investigating the mechanism and the prevention of this cancer. We found that the type of mutations induced by two 2-mg/kg subcutaneous injections of NMBA in the lacI gene of "Big Blue" rats is consistent with that found previously for nitrosamines in other systems and consists of G:C-->A:T transitions. We report that the addition of ellagic acid to the feed, replacing drinking water with green tea, and gavage with DAS significantly reduced the mutagenicity of NMBA. In contrast, the addition of 5% ethanol to the drinking water increased the mutagenicity of NMBA. This is consistent with findings that these compounds modulate NMBA-induced carcinogenesis in the rat.
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Affiliation(s)
- Johan G de Boer
- Centre for Biomedical Research, University of Victoria, Victoria BC, Canada.
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17
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Affiliation(s)
- Alexander Gosslau
- Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854-8087, USA.
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18
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Abstract
Columnar-lined lower esophagus (CLE) or Barrett's esophagus (BE) is caused by chronic reflux of the gastrointestinal tract and can progress to invasive adenocarcinoma. However, the pathophysiology, cell of origin, and management of this condition is incompletely understood. This review evaluates the role of in vivo models in resolving these debates. A search was performed on the Ovid and Pub Medline for 1964-2001 and Cochrane Collaboration. The keywords used were adenocarcinoma, animal model, Barrett's esophagus, columnar-lined esophagus, esophageal neoplasms, and esophageal carcinogenesis. All relevant papers were scrutinized and an attempt at tabulation was made. In vivo models have been used at several stages of debate on the pathophysiology of BE. They provide conclusive evidence for its acquired nature secondary to duodenogastroesophageal reflux. The cell of origin of experimental BE may arise from adjacent columnar epithelium, basal layer multipotent cells, or esophageal glands. Experimental work on BE is lacking in assessing therapeutic modalities.
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Affiliation(s)
- Y Koak
- Department of Surgery, Royal Free and University College School of Medicine, Rowland Hill Street, London, UK.
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19
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Catterall F, Copeland E, Clifford MN, Ioannides C. Effects of black tea theafulvins on aflatoxin B(1) mutagenesis in the Ames test. Mutagenesis 2003; 18:145-50. [PMID: 12621070 DOI: 10.1093/mutage/18.2.145] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Black tea theafulvins, a fraction of thearubigins isolated from black tea aqueous infusions, potentiated the mutagenic activity of the mycotoxin aflatoxin B(1) in the Ames test, in the presence of a hepatic S9 activation system derived from Aroclor 1254-treated rats. In contrast, when the S9 activation system was replaced with isolated microsomes, theafulvins suppressed the mutagenicity of the mycotoxin. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, incorporation of the theafulvins into the activation system reduced the mutagenic activity, whereas if it was added before termination of microsomal activity a potentiation of mutagenic response was observed. In in vitro studies, theafulvins inhibited epoxide hydrolase and glutathione S-transferase activities in a concentration-dependent manner. Finally, the mutagenicity of aflatoxin B(1) was much more pronounced in bacteria that were pre-exposed to theafulvins but from which they were subsequently washed off. It may be inferred from the above studies that the genotoxic synergy between aflatoxin B(1) and black tea theafulvins does not occur during the bioactivation of the carcinogen, but may partly be due to decreased deactivation of the reactive intermediate, aflatoxin B(1) 8,9-oxide, by conjugation with glutathione.
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Affiliation(s)
- Fenton Catterall
- School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
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20
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Yaping Z, Wenli Y, Dapu W, Xiaofeng L, Tianxi H. Chemiluminescence determination of free radical scavenging abilities of ‘tea pigments’ and comparison with ‘tea polyphenols’. Food Chem 2003. [DOI: 10.1016/s0308-8146(02)00241-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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21
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Murugesan G, Angayarkanni J, Swaminathan K. Effect of tea fungal enzymes on the quality of black tea. Food Chem 2002. [DOI: 10.1016/s0308-8146(02)00157-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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22
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Angayarkanni J, Palaniswamy M, Murugesan S, Swaminathan K. Improvement of tea leaves fermentation with Aspergillus spp. pectinase. J Biosci Bioeng 2002. [DOI: 10.1016/s1389-1723(02)80167-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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23
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Yang CS, Yang GY, Chung JY, Lee MJ, Li C. Tea and tea polyphenols in cancer prevention. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2002; 492:39-53. [PMID: 11480674 DOI: 10.1007/978-1-4615-1283-7_5] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- C S Yang
- Laboratory for Cancer Research, College of Pharmacy Rutgers, The State University of New Jersey, Piscataway 08854, USA
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24
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Abstract
Tea has received a great deal of attention because tea polyphenols are strong antioxidants, and tea preparations have inhibitory activity against tumorigenesis. The bioavailability and biotransformation of tea polyphenols, however, are key factors limiting these activities in vivo. The inhibition of tumorigenesis by green or black tea preparations has been demonstrated in animal models on different organ sites such as skin, lung, oral cavity, esophagus, forestomach, stomach, small intestine, colon, pancreas, and mammary gland. Epidemiological studies, however, have not yielded clear conclusions concerning the protective effects of tea consumption against cancer formation in humans. The discrepancy between the results from humans and animal models could be due to 1) the much higher doses of tea used in animals in comparison to human consumption, 2) the differences in causative factors between the cancers in humans and animals, and 3) confounding factors limiting the power of epidemiological studies to detect an effect. It is possible that tea may be only effective against specific types of cancer caused by certain etiological factors. Many mechanisms have been proposed for the inhibition of carcinogenesis by tea, including the modulation of signal transduction pathways that leads to the inhibition of cell proliferation and transformation, induction of apoptosis of preneoplastic and neoplastic cells, as well as inhibition of tumor invasion and angiogenesis. These mechanisms need to be evaluated and verified in animal models or humans in order to gain more understanding on the effect of tea consumption on human cancer.
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Affiliation(s)
- Chung S Yang
- Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8020, USA.
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25
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Yang CS, Landau JM, Huang MT, Newmark HL. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr 2001; 21:381-406. [PMID: 11375442 DOI: 10.1146/annurev.nutr.21.1.381] [Citation(s) in RCA: 778] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Plants consumed by humans contain thousands of phenolic compounds. The effects of dietary polyphenols are of great current interest due to their antioxidative and possible anticarcinogenic activities. A popular belief is that dietary polyphenols are anticarcinogens because they are antioxidants, but direct evidence for this supposition is lacking. This chapter reviews the inhibition of tumorigenesis by phenolic acids and derivatives, tea and catechins, isoflavones and soy preparations, quercetin and other flavonoids, resveratrol, and lignans as well as the mechanisms involved based on studies in vivo and in vitro. Polyphenols may inhibit carcinogenesis by affecting the molecular events in the initiation, promotion, and progression stages. Isoflavones and lignans may influence tumor formation by affecting estrogen-related activities. The bioavailability of the dietary polyphenols is discussed extensively, because the tissue levels of the effective compounds determine the biological activity. Understanding the bioavailability and blood and tissue levels of polyphenols is also important in extrapolating results from studies in cell lines to animal models and humans. Epidemiological studies concerning polyphenol consumption and human cancer risk suggest the protective effects of certain food items and polyphenols, but more studies are needed for clear-cut conclusions. Perspectives on the application of dietary polyphenols for the prevention of human cancer and possible concerns on the consumption of excessive amounts of polyphenols are discussed.
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Affiliation(s)
- C S Yang
- Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
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26
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Abstract
Squamous cell carcinoma (SCC) of the human esophagus has a multifactorial etiology involving several environmental and/or genetic factors. Current modalities of therapy for this disease offer poor survival and cure rates. Although a number of approaches could be undertaken to reduce the occurrence of esophageal SCC, including changes in lifestyle and improved nutrition, such approaches are not easily implemented. Chemoprevention offers a viable alternative that is likely to be effective against this disease. Clinical investigations in areas of high incidence of esophageal SCC have shown that primary chemoprevention of this disease is feasible, if potent inhibitors are identified. Studies in the Fischer 344 rat model of nitrosamine-induced tumorigenesis have proven valuable in understanding the biology of esophageal SCCs and help identify surrogate end-point biomarkers and putative agents that can be useful in human chemoprevention studies. Several compounds that inhibit tumor initiation by suspected human esophageal carcinogens have been identified using this model. These include diallyl sulfide, isothiocyanates and several polyphenolic compounds. Novel biomarkers, including nuclear/nucleolar morphometry using computer-assisted image analysis of preneoplastic lesions, have been developed to measure efficacy of chemopreventive agents against esophageal SCC. The identification of single agents that inhibit the progression of dysplastic lesions, however, has proven difficult. Results from a food-based approach suggest that the use of freeze-dried berry preparations can affect both initiation and promotion/progression of esophageal SCC in an animal model. These observations provide valuable information for future studies on chemoprevention of cancers of the esophagus in a clinical setting. Given the complex etiology of esophageal SCC, it is felt that the most effective chemoprevention strategies would include agents that reduce mutational events associated with carcinogen exposure in combination with agents that inhibit the progression of intraepithelial dysplasia to invasive cancer.
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Affiliation(s)
- G D Stoner
- Division of Environmental Health Sciences, The Ohio State University School of Public Health, Columbus, OH 43210, USA.
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27
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Liao S, Kao YH, Hiipakka RA. Green tea: biochemical and biological basis for health benefits. VITAMINS AND HORMONES 2001; 62:1-94. [PMID: 11345896 DOI: 10.1016/s0083-6729(01)62001-6] [Citation(s) in RCA: 111] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- S Liao
- Tang Center for Herbal Medicine Research, Ben May Institute for Cancer Research, and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA
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28
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Jia XD, Han C. Chemoprevention of tea on colorectal cancer induced by dimethylhydrazine in Wistar rats. World J Gastroenterol 2000; 6:699-703. [PMID: 11819677 PMCID: PMC4688846 DOI: 10.3748/wjg.v6.i5.699] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2000] [Revised: 06/16/2000] [Accepted: 06/23/2000] [Indexed: 02/06/2023] Open
Abstract
AIM:To investigate the chemopreventive effects of green tea and tea pigment on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis.METHODS:Male weaning Wistar rats were randomly allocated into four groups.Rats in the positive control group were given a(c)s.c. injection of DMH, once a week for ten weeks;rats in tea treated groups, with the same DMH treatment as in the positive group, received 2% green tea and 0.1% tea pigments; rats in the negative control group were given s.c.injection of the same volume of saline as well as DMH in the positive group. Animals were sacrified and necropsied at the end of week 16 and week 32.RESULTS:Aberrant cryptic foci (ACF) were formed in animals in DMH-treated groups at the end of week 16. Compared to the DMH group, green tea and tea pigments groups had less ACF (148.25 and 204.25, respectively, P<0.01). At the end of week 32, all rats in DMH group developed large intestinal tumors. The results also showed that DMH increased labeling index (LI) of proliferating cell nuclear antigen (PCNA) of intestinal mucosa and the expression of ras-p21. However, in the tea-treated groups, PCNA-LI was significantly reduced as compared with the positive control group (36.63 and 40.36 in the green tea group and tea pigment group, respectively, at the end of the experiment,P<0.01).ras-p21 expression was also significantly reduced (2.07 and 2.36 in the colon tumors of rats in the green tea group and tea pigments group, respectively at the end of the experiment, P<0.01). Furthermore, green tea and tea pigment inhibited the expression of Bcl-2 protein (2, 5, 1, 0 and 2, 4, 1, 0,respectively, at the end of the experiment P<0.01), and induced expression of Bax protein (0,1,3,4 and 0,1,4,3, respectively, P <0.01).CONCLUSION:Chinese green tea drinking inhibited ACF and colonic tumors formation in rats, which showed that tea had a significant chemopreventive effect on DMH-induced colorectal carcinogenesis. Such effects may be due to suppression of cell proliferation and induction of apoptosis in the intestinal crypts.
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29
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Abstract
Plant flavonoids are common dietary components that have many potent biological properties. Early studies of these compounds investigated their mutagenic and genotoxic activity in a number of in vitro assays. Recently, a renewed interest in flavonoids has been fueled by the antioxidant and estrogenic effects ascribed to them. This has led to their proposed use as anticarcinogens and cardioprotective agents, prompting a dramatic increase in their consumption as dietary supplements. Unfortunately, the potentially toxic effects of excessive flavonoid intake are largely ignored. At higher doses, flavonoids may act as mutagens, pro-oxidants that generate free radicals, and as inhibitors of key enzymes involved in hormone metabolism. Thus, in high doses, the adverse effects of flavonoids may outweigh their beneficial ones, and caution should be exercised in ingesting them at levels above that which would be obtained from a typical vegetarian diet. The unborn fetus may be especially at risk, since flavonoids readily cross the placenta. More research on the toxicological properties of flavonoids is warranted given their increasing levels of consumption.
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Affiliation(s)
- C F Skibola
- Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, 94720-7360, USA
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30
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Damianaki A, Bakogeorgou E, Kampa M, Notas G, Hatzoglou A, Panagiotou S, Gemetzi C, Kouroumalis E, Martin PM, Castanas E. Potent inhibitory action of red wine polyphenols on human breast cancer cells. J Cell Biochem 2000; 78:429-41. [PMID: 10861841 DOI: 10.1002/1097-4644(20000901)78:3<429::aid-jcb8>3.0.co;2-m] [Citation(s) in RCA: 191] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Breast cancer (one of the most common malignancy in Western societies), as well as esophagus, stomach, lung, bladder, and prostate cancer, depend on environmental factors and diet for growth and evolution. Dietary micronutriments have been proposed as effective inhibitory agents for cancer initiation, progression, and incidence. Among them, polyphenols, present in different foods and beverages, have retained attention in recent years. Red wine is a rich source of polyphenols, and their antioxidant and tumor arresting effects have been demonstrated in different in vitro and in vivo systems. In the present study, we have measured the antiproliferative effect of red wine concentrate, its total polyphenolic pool, and purified catechin, epicatechin, quercetin, and resveratrol, which account for more than 70% of the total polyphenols in red wine, on the proliferation of hormone sensitive (MCF7, T47D) and resistant (MDA-MB-231) breast cancer cell lines. Our results indicate that polyphenols, at the picomolar or the nanomolar range, decrease cell proliferation in a dose- and a time-dependant manner. In hormone sensitive cell lines, a specific interaction of each polyphenol with steroid receptors was observed, with IC(50)s lower than previously described. Interaction of polyphenols with steroid receptors cannot fully explain their inhibitory effect on cell proliferation. In addition, discrete antioxidant action on each cell line was detected under the same concentrations, both by modifying the toxic effect of H(2)O(2), and the production of reactive oxygen species (ROS), after phorbol ester stimulation. Our results suggest that low concentrations of polyphenols, and consecutively, consumption of wine, or other polyphenol-rich foods and beverages, could have a beneficial antiproliferative effect on breast cancer cell growth.
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Affiliation(s)
- A Damianaki
- Laboratory of Experimental Endocrinology, University of Crete, School of Medicine and University Hospital, Heraklion, Greece
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31
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Abstract
The inhibitory action of tea (Camellia sinensis) and tea components against cancer formation has been demonstrated in different animal models involving different organ sites in many laboratories. The possible preventive activity of tea against cancer in humans, however, is not clear. A critical question is whether the information obtained from animal studies is applicable to humans because of possible species differences or the difference in the quantity of tea used in animal studies and that consumed by humans. This article will discuss the results from animal studies and possible cancer inhibitory mechanisms that might be applicable to human cancer prevention. To provide a basis for more quantitative analyses of the effect of tea on carcinogenesis, the levels of tea polyphenols in blood, urine and tissue samples have been analyzed, and the pharmacokinetic properties of tea polyphenols studied. Studies with cell lines have demonstrated that tea polyphenols affect signal transduction pathways, inhibit cell proliferation and induce apoptosis, but the effective concentrations are usually much higher than those observed in blood and tissues. More mechanistic studies in these areas will help us to understand the inhibitory action of tea against carcinogenesis and provide background for evaluating the effects of tea consumption on human carcinogenesis.
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Affiliation(s)
- C S Yang
- Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08854, USA
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