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Ferrer RA, Chen BY, Garcia JPT, Rejano CJF, Tsai PW, Hsueh CC, Tayo LL. Deciphering the Regulatory Potential of Antioxidant and Electron-Shuttling Bioactive Compounds in Oolong Tea. BIOLOGY 2025; 14:487. [PMID: 40427676 PMCID: PMC12109060 DOI: 10.3390/biology14050487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/25/2025] [Accepted: 04/25/2025] [Indexed: 05/29/2025]
Abstract
OT has gained attention for its high polyphenol content and therapeutic potential. To elucidate this further, this study investigated the electron-shuttling bioactive compounds of OT and evaluated their effect on dysregulated breast cancer (BC) genes. OT extracts were obtained via solvent extraction (SE) and supercritical fluid extraction (SFE), followed by in vitro assays. Phytochemical analysis revealed that ethanol-extracted OT (OTL-E) had the highest polyphenol, flavonoid, and tannin contents, correlating with strong antioxidant activity, while water-extracted OT (OTL-W) exhibited greater bioelectricity-stimulating properties in microbial fuel cells (MFC), confirmed by cyclic voltammetry (CV). Based on phytochemical analyses, SE displayed a better extraction technique for isolating OT bioactive compounds compared to SFE. In silico approaches through network pharmacology, molecular docking and dynamics simulations revealed that polyphenols with ortho- or para-dihydroxyl groups targeted dysregulated BC proteins involved in kinase signaling, apoptosis, and hormone receptor pathways. Luteolin exhibited the highest binding affinities to MAPK1 and PIK3CA with free energy (ΔG) of -9.1 and -8.4 kcal/mol, respectively. Trajectory-based analyses confirmed enthalpy-favored ligand-induced conformational changes to these oncoproteins, altering their function in BC development. These findings suggest the potential of OT as a bioelectricity-stimulating and chemopreventive agent, warranting further in vitro and in vivo validation.
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Affiliation(s)
- Regineil A. Ferrer
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila 1002, Philippines; (R.A.F.); (J.P.T.G.); (C.J.F.R.)
- School of Graduate Studies, Mapúa University, Manila 1002, Philippines
| | - Bor-Yann Chen
- Department of Chemical and Materials Engineering, National I-lan University, I-lan 260, Taiwan; (B.-Y.C.); (C.-C.H.)
| | - Jon Patrick T. Garcia
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila 1002, Philippines; (R.A.F.); (J.P.T.G.); (C.J.F.R.)
- School of Graduate Studies, Mapúa University, Manila 1002, Philippines
| | - Christine Joyce F. Rejano
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila 1002, Philippines; (R.A.F.); (J.P.T.G.); (C.J.F.R.)
- School of Graduate Studies, Mapúa University, Manila 1002, Philippines
| | - Po-Wei Tsai
- Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan;
| | - Chung-Chuan Hsueh
- Department of Chemical and Materials Engineering, National I-lan University, I-lan 260, Taiwan; (B.-Y.C.); (C.-C.H.)
| | - Lemmuel L. Tayo
- Department of Biology, School of Health Sciences, Mapúa University, Makati 1200, Philippines
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Khan J. Optical Chemosensors Synthesis and Appplication for Trace Level Metal Ions Detection in Aqueous Media: A Review. J Fluoresc 2025; 35:561-582. [PMID: 38175458 DOI: 10.1007/s10895-023-03559-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/19/2023] [Indexed: 01/05/2024]
Abstract
In recent years, the development of optical chemosensors for the sensitive and selective detection of trace level metal ions in aqueous media has garnered significant attention within the scientific community. This review article provides a comprehensive overview of the synthesis strategies and applications of optical chemosensors dedicated to the detection of metal ions at low concentrations in water-based environments. The discussion encompasses a wide range of metal ions, including but not limited to heavy metals, transition metals, and rare earth elements, emphasizing their significance in environmental monitoring, industrial processes, and biological systems. The review explores into the synthesis methodologies employed for designing optical chemosensors, discovering diverse materials like organic dyes, nanoparticles, polymers, and hybrid materials. Special attention is given to the design principles that enable the selective recognition of specific metal ions, highlighting the role of ligand chemistry, coordination interactions, and structural modifications. Furthermore, the article thoroughly surveys the analytical performance of optical chemosensors in terms of sensitivity, selectivity, response time, and detection limits. Real-world applications, including water quality assessment, environmental monitoring, and biomedical diagnostics, are extensively covered to underscore the practical relevance of these sensing platforms. Additionally, the review sheds light on emerging trends, challenges, and future prospects in the field, providing insights into potential advancements and innovations. By synthesizing the current state of knowledge on optical chemosensors for trace level metal ions detection. The collective information presented herein not only offers a comprehensive understanding of the existing technologies but also inspires future research endeavors to address the evolving demands in the realm of trace metal ion detection.
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Affiliation(s)
- Jehangir Khan
- Department of Chemistry, University of Malakand, Chakdara, Dir (Lower), Khyber Pakhtunkhwa, Pakistan.
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Datta S, Ghosh S, Bishayee A, Sinha D. Flexion of Nrf2 by tea phytochemicals: A review on the chemopreventive and chemotherapeutic implications. Pharmacol Res 2022; 182:106319. [PMID: 35732198 DOI: 10.1016/j.phrs.2022.106319] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 06/16/2022] [Accepted: 06/16/2022] [Indexed: 01/11/2023]
Abstract
Nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2), the redox-sensitive transcription factor, plays a key role in stress-defense and detoxification. Nrf2 is tightly controlled by its negative regulator cum sensor Kelch-[ECH]-associated protein 1 (Keap1). Nrf2 is well known for its dual nature owing to its cancer preventive and cancer promoting abilities. Modulation of this biphasic nature of Nrf2 signaling by phytochemicals may be a potential cancer preventive and anticancer therapeutic strategy. Phytocompounds may either act as Nrf2-activator or Nrf2-inhibitor depending on their differential concentration and varied cellular environment. Tea is not just the most popular global beverage with innumerable health-benefits but has well-established chemopreventive and chemotherapeutic effects. Various types of tea infusions contain a wide range of bioactive compounds, such as polyphenolic catechins and flavonols, which are endowed with potent antioxidant properties. Despite of their rapid biotransformation and poor bioavailability, regular tea consumption is risk-reductive for several cancer forms. Tea catechins show their dual Nrf2-modulatory effect by directly acting on Nrf2-Keap1 or their upstream regulators and downstream effectors in a highly case-specific manner. In this review, we have tried to present a comprehensive evaluation of the Nrf2-mediated chemopreventive and chemotherapeutic applications of tea in various preclinical cancer models, the Nrf2-modulatory mechanisms, and the limitations which need to be addressed in future research.
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Affiliation(s)
- Suchisnigdha Datta
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata - 700 026, West Bengal, India
| | - Sukanya Ghosh
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata - 700 026, West Bengal, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.
| | - Dona Sinha
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata - 700 026, West Bengal, India.
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Wen S, An R, Li DL, Cao JX, Li Z, Zhang W, Chen R, Li Q, Lai X, Sun L, Sun S. Tea and Citrus maxima complex induces apoptosis of human liver cancer cells via PI3K/AKT/mTOR pathway in vitro. CHINESE HERBAL MEDICINES 2022; 14:449-458. [PMID: 36118010 PMCID: PMC9476756 DOI: 10.1016/j.chmed.2021.09.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 07/08/2021] [Accepted: 09/05/2021] [Indexed: 11/25/2022] Open
Abstract
Objective In this study, black tea and Citrus maxima (BT-CM), yellow tea and C. maxima (YT-CM), green tea and C. maxima (GT-CM) as subjects, the active ingredient content and antioxidant activity of three tea and C. maxima (T-CM) were analyzed. The effects of three T-CMs on apoptosis of liver cells in vitro and its mechanism were further explored. Methods National standard method and HPLC were used for active ingredient analysis. MTT, cell flow cytometry and Western blot were used to analyze the effects of three T-CMs on cell proliferation, apoptosis, and its underlying molecular mechanism. Results The content of tea polyphenols, free amino acids, ratio of polyphenols and amino acids, ester catechins, non-ester catechins and caffeine in YT-CM and GT-CM was significantly higher than that of BT-CM. The in vitro antioxidant capacity of YT-CM and GT-CM was also significantly stronger than that of BT-CM. Three T-CMs had the effects of inhibiting proliferation, arresting cell cycle and inducing apoptosis in HepG2 and Bel7402 cells, especially YT-CM and GT-CM. Western blot analysis showed three T-CMs activated PI3K/AKT/mTOR signaling pathway and regulated the expression levels of apoptosis-related proteins Bax, Bcl-2 and Caspase-3/9. YT-CM and GT-CM had better ability to change the signal pathway than BT-CM. Conclusion In short, T-CMs, which combined different degrees of fermentation tea with C. maxima, were rich in nutrients and biologically active substances. T-CMs, especially YT-CM and GT-CM, are healthy drinks that help to prevent and treat liver cancer.
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Luo T, Jiang JG. Anticancer Effects and Molecular Target of Theaflavins from Black Tea Fermentation in Vitro and in Vivo. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:15052-15065. [PMID: 34878780 DOI: 10.1021/acs.jafc.1c05313] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Black tea is one of the most popular beverages in the world, and numerous epidemiological studies have shown that drinking black tea is good for health. As a natural tea pigment formed during the fermentation of black tea, the content of theaflavins accounts for only 2-6% of the dry weight of black tea, but they have a great impact on the color and taste of black tea soup. Recently, a large number of studies have shown that theaflavins have a significant anticancer effect. In this Perspective, we first state the physical and chemical properties, separation and purification methods, and biological formation pathways of theaflavins and analyze their safety and oral bioavailability and the structure-activity relationship of their antioxidant and anticancer activities; then, we describe in detail their anticancer effect in vitro and in vivo and highlight their various molecular targets involved in cancer inhibition. The anticancer molecular targets of theaflavins are mainly cell-cycle regulatory proteins, apoptosis-related proteins, cell-migration-related proteins, and growth transcription factors. Finally, the possibility of developing new health-care food based on theaflavins is discussed. This Perspective is expected to provide a theoretical basis for the anticancer application of theaflavins in the future.
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Affiliation(s)
- Ting Luo
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China
| | - Jian-Guo Jiang
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China
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Kapoor B, Gulati M, Gupta R, Singh SK, Gupta M, Nabi A, Chawla PA. A Review on Plant Flavonoids as Potential Anticancer Agents. CURR ORG CHEM 2021. [DOI: 10.2174/1385272824999201126214150] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Flavonoids are polyphenolic compounds that are mainly derived from fruits and
vegetables and constitute an essential part of plant-derived beverages such as green tea, wine
and cocoa-based products. They have been shown to possess anticancer effects via different
mechanisms such as carcinogen inactivation, antiproliferation, cell cycle arrest, induction of
apoptosis and differentiation, inhibition of angiogenesis, anti-oxidation and reversal of
multidrug resistance or a combination of any two or more of these mechanisms. The present
review summarizes the chemistry, biosynthesis and anticancer evaluation of flavonoids in
both animal and human studies. A special emphasis has been placed on the flavonoids that are
being screened in different phases of clinical trials for chemoprotective action against various
cancers.
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Affiliation(s)
- Bhupinder Kapoor
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH 1) Phagwara, Punjab 144411, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH 1) Phagwara, Punjab 144411, India
| | - Reena Gupta
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH 1) Phagwara, Punjab 144411, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH 1) Phagwara, Punjab 144411, India
| | - Mukta Gupta
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH 1) Phagwara, Punjab 144411, India
| | - Arshid Nabi
- Department of Chemistry, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Pooja A. Chawla
- Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, Ghal Kalan Moga, Punjab 142001, India
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Boukhatem MN, Setzer WN. Aromatic Herbs, Medicinal Plant-Derived Essential Oils, and Phytochemical Extracts as Potential Therapies for Coronaviruses: Future Perspectives. PLANTS (BASEL, SWITZERLAND) 2020; 9:E800. [PMID: 32604842 PMCID: PMC7356962 DOI: 10.3390/plants9060800] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/29/2020] [Accepted: 06/24/2020] [Indexed: 01/08/2023]
Abstract
After its recent discovery in patients with serious pneumonia in Wuhan (China), the 2019 novel coronavirus (2019-nCoV), named also Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spread quickly. Unfortunately, no drug or vaccine for treating human this coronavirus infection is available yet. Numerous options for controlling or preventing emerging 2019-nCoV infections may be predicted, including vaccines, interferon therapies, and small-molecule drugs. However, new interventions are likely to require months to years to develop. In addition, most of the existing antiviral treatments frequently lead to the development of viral resistance combined with the problem of side effects, viral re-emergence, and viral dormancy. The pharmaceutical industry is progressively targeting phytochemical extracts, medicinal plants, and aromatic herbs with the aim of identifying lead compounds, focusing principally on appropriate alternative antiviral drugs. Spices, herbal medicines, essential oils (EOs), and distilled natural products provide a rich source of compounds for the discovery and production of novel antiviral drugs. The determination of the antiviral mechanisms of these natural products has revealed how they interfere with the viral life cycle, i.e., during viral entry, replication, assembly, or discharge, as well as virus-specific host targets. Presently, there are no appropriate or approved drugs against CoVs, but some potential natural treatments and cures have been proposed. Given the perseverance of the 2019-nCoV outbreak, this review paper will illustrate several of the potent antiviral chemical constituents extracted from medicinal and aromatic plants, natural products, and herbal medicines with recognized in vitro and in vivo effects, along with their structure-effect relationships. As this review shows, numerous potentially valuable aromatic herbs and phytochemicals are awaiting assessment and exploitation for therapeutic use against genetically and functionally different virus families, including coronaviruses.
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Affiliation(s)
- Mohamed Nadjib Boukhatem
- Département de Biologie et Physiologie Cellulaire, Faculté des Sciences de la Nature et de la Vie, Université - Saad Dahlab - Blida 1, BP 270, Blida 09000, Algeria
| | - William N. Setzer
- Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA;
- Aromatic Plant Research Center, 230 N 1200 E, Suite 100, Lehi, UT 84043, USA
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Maity R, Chatterjee M, Banerjee A, Das A, Mishra R, Mazumder S, Chanda N. Gold nanoparticle-assisted enhancement in the anti-cancer properties of theaflavin against human ovarian cancer cells. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 104:109909. [PMID: 31499983 DOI: 10.1016/j.msec.2019.109909] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 06/01/2019] [Accepted: 06/20/2019] [Indexed: 12/20/2022]
Abstract
Redox-active quinones have been reported to show good potential for biological activities, while efforts are directed to explore the usefulness of these materials further in cancer management. Our previous study demonstrated that theaflavin and theaflavin-gallates (tea-extracted polyphenols) selectively induce apoptosis of tumour cells in vitro, but its concentration for showing half-maximal therapeutic response remains a matter of concern. In this report, we demonstrated that if theaflavin is conjugated with gold nanoparticles (AuNPs) to form a nanoconjugate AuNP@TfQ, its apoptotic ability increases significantly in comparison to the bare theaflavin (Tf). The nanoconjugate is prepared by following a one-step green synthesis ̶ a reaction between HAuCl4 and the aflavin at room temperature. AuNP@TfQ is characterized using particle size analysis, FESEM, UV-vis, FTIR, fluorescence, and X-ray photoelectron spectroscopytechniques. We assume that the enhanced anti-cancer effect of AuNP@TfQ appears due to the facile oxidation of the pristine theaflavin to its quinone derivative on the surface of AuNPs. The presence of quinone motif in AuNP@TfQ induces an increased level of ROS generation probably through the depolarization of mitochondria and resulted in the caspase-mediated apoptotic cell death which may hold the potential for a "magic bullet"-mediated ovarian cancer treatment.
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Affiliation(s)
- Ritwik Maity
- Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India
| | - Manosree Chatterjee
- Materials Processing and Microsystems Laboratory, Central Mechanical Engineering Research Institute, Mahatma Gandhi Rd, Durgapur, West Bengal 713209, India
| | - Anmol Banerjee
- Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India
| | - Amlan Das
- Department of Chemistry, National Institute of Technology Sikkim, Barfung Block, Ravangla, Sikkim 737139, India
| | - Raghwendra Mishra
- Department of Physiology, Ananda Mohan College, 102/1, Raja Ram Mohan Sarani, College Street, Kolkata, West Bengal 700009, India.
| | - Santasree Mazumder
- Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India.
| | - Nripen Chanda
- Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India; Materials Processing and Microsystems Laboratory, Central Mechanical Engineering Research Institute, Mahatma Gandhi Rd, Durgapur, West Bengal 713209, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development Centre, (CSIR-HRDC) Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 201 002, India.
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Dhatwalia SK, Kumar M, Dhawan DK. Role of EGCG in Containing the Progression of Lung Tumorigenesis - A Multistage Targeting Approach. Nutr Cancer 2018; 70:334-349. [PMID: 29570987 DOI: 10.1080/01635581.2018.1445762] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lung cancer is a prominent form among various types of cancers, irrespective of the sex worldwide. Treatment of lung cancer involves the intensive phase of chemotherapy/radiotherapy which is associated with high rate of adverse events. There is a need of safe and reliable treatment/adjunctive therapy to apprehend the cancer by reducing the undesirable outcome of primary therapy. Epigallocatechin-3-gallate (EGCG), which is a potent antioxidant and anticancer compound extracted from the plant camellia sinensis has proved to be a novel agent to control or reduce lung tumorigenesis by affecting the signaling molecules of cell cycle regulation and apoptotic pathways. In vitro studies have revealed that EGCG can contain carcinogenesis by altering the molecules involved in multiple signal transduction pathways like ERK, VEGF, COX2, NEAT, Ras-GTPase, and kinases. The animal studies have also demonstrated effectiveness of EGCG by inhibiting various molecular pathways which include AKT, NFkB, MAPK, Bcl/Bax, DNMT1, and HIF-1α. Various attempts have been made to see the adjunctive role of EGCG in human lung cancer. Phase I/II clinical studies have recommended that EGCG is quite safe and effective in providing protection against cancer. In this review, we will discuss the role of EGCG and its molecular mechanisms in lung carcinogenesis.
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Affiliation(s)
| | | | - Devinder K Dhawan
- a Department of Biophysics , Panjab University , Chandigarh , India.,c Nuclear Medicine, Panjab University , Chandigarh , India
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Pan H, Wang F, Rankin GO, Rojanasakul Y, Tu Y, Chen YC. Inhibitory effect of black tea pigments, theaflavin‑3/3'-gallate against cisplatin-resistant ovarian cancer cells by inducing apoptosis and G1 cell cycle arrest. Int J Oncol 2017; 51:1508-1520. [PMID: 29048667 PMCID: PMC5642389 DOI: 10.3892/ijo.2017.4145] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 09/26/2017] [Indexed: 12/26/2022] Open
Abstract
Adverse side effects and acquired resistance to conventional chemotherapy based on platinum drive the exploration of other selective anticancer drugs. Theaflavin-3-gallate (TF2a) and theaflavin-3′-gallate (TF2b), theaflavin monomers in black tea, exhibited a potent growth inhibitory effect on cisplatin-resistant ovarian cancer A2780/CP70 cells and were less cytotoxic to normal ovarian IOSE-364 cell line. Flow cytometry analysis and western blotting indicated that TF2a and TF2b induced apoptosis and G1 cell cycle arrest in ovarian cancer A2780/CP70 cells. Hoechst 33342 staining was used to confirm the apoptotic effect. Downregulation of CDK2 and CDK4 for TF2a and CDK2 and cyclin E1 for TF2b led to the accumulation of cells in G1 phase. TF2a and TF2b induced apoptosis and G1 through p53-dependent pathways. TF2a and TF2b induced DNA damage through ATM/Chk/p53 pathway. TF2a and TF2b also induced inhibition of A2780/CP70 cells through Akt and MAPK pathways. The results of this study implied that TF2a and TF2b might help prevent and treat platinum-resistant ovarian cancer.
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Affiliation(s)
- Haibo Pan
- Department of Tea Science, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Fang Wang
- Department of Tea Science, Wuyi University, Wuyishan, Fujian, P.R. China
| | - Gary O Rankin
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Yon Rojanasakul
- Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, USA
| | - Youying Tu
- Department of Tea Science, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Yi Charlie Chen
- College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV, USA
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Zhang J, Cai S, Li J, Xiong L, Tian L, Liu J, Huang J, Liu Z. Neuroprotective Effects of Theaflavins Against Oxidative Stress-Induced Apoptosis in PC12 Cells. Neurochem Res 2016; 41:3364-3372. [PMID: 27686660 DOI: 10.1007/s11064-016-2069-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/08/2016] [Accepted: 09/21/2016] [Indexed: 11/28/2022]
Abstract
Oxidative stress can induce neuronal apoptosis via the production of superoxide and hydroxyl radicals. This process is as a major pathogenic mechanism in neurodegenerative disorders. In this study, we aimed to clarify whether theaflavins protect PC12 cells from oxidative stress damage induced by H2O2. A cell model of PC12 cells undergoing oxidative stress was created by exposing cells to 200 μM H2O2 in the presence or absence of varying concentrations of theaflavins (5, 10, and 20 μM). Cell viability was monitored using the MTT assay and Hoechst 33258 staining, showing that 10 μM theaflavins enhanced cell survival following 200 μM H2O2 induced toxicity and increased cell viability by approximately 40 %. Additionally, we measured levels of intracellular reactive oxygen species (ROS) and antioxidant enzyme activity. This suggested that the neuroprotective effect of theaflavins against oxidative stress in PC12 cells is derived from suppression of oxidant enzyme activity. Furthermore, Western blot analyses indicated that theaflavins downregulated the ratio of pro-apoptosis/anti-apoptosis proteins Bax/Bcl-2. Theaflavins also downregulated the expression of caspase-3 compared with a H2O2-treated group that had not been treated with theaflavins. Interestingly, this is the first study to report that the four main components of theaflavins found in black tea can protect neural cells (PC12) from apoptosis induced by H2O2. These findings provide the foundations for a new field of using theaflavins or its source, black tea, in the treatment of neurodegenerative diseases caused by oxidative stress.
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Affiliation(s)
- Jing Zhang
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China
| | - Shuxian Cai
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China
| | - Juan Li
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China
| | - Ligui Xiong
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China
| | - Lili Tian
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China
| | - Jianjun Liu
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China
| | - Jianan Huang
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China. .,National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Changsha, 410128, China. .,Collaborative Innovation Center of Utilization of Functional Ingredients from Botanicals, Changsha, 410128, China.
| | - Zhonghua Liu
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, 410128, China. .,National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Changsha, 410128, China. .,Collaborative Innovation Center of Utilization of Functional Ingredients from Botanicals, Changsha, 410128, China.
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Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies. Br J Nutr 2015. [PMID: 26202661 DOI: 10.1017/s0007114515002329] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Epidemiological studies have demonstrated inconsistent associations between tea consumption and mortality of all cancers, CVD and all causes. To obtain quantitative overall estimates, we conducted a dose-response meta-analysis of prospective cohort studies. A literature search in PubMed and Embase up to April 2015 was conducted for all relevant papers published. Random-effects models were used to calculate pooled relative risks (RR) with 95 % CI. In eighteen prospective studies, there were 12 221, 11 306 and 55 528 deaths from all cancers, CVD and all causes, respectively. For all cancer mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 1·06 (95 % CI 0·98, 1·15) and 0·79 (95 % CI 0·65, 0·97), respectively. For CVD mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·67 (95 % CI 0·46, 0·96) and 0·88 (95 % CI 0·77, 1·01), respectively. For all-cause mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·80 (95 % CI 0·68, 0·93) and 0·90 (95 % CI 0·83, 0·98), respectively. The dose-response analysis indicated that one cup per d increment of green tea consumption was associated with 5 % lower risk of CVD mortality and with 4 % lower risk of all-cause mortality. Green tea consumption was significantly inversely associated with CVD and all-cause mortality, whereas black tea consumption was significantly inversely associated with all cancer and all-cause mortality.
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Ge GZ, Xu TR, Chen C. Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms. Acta Biochim Biophys Sin (Shanghai) 2015; 47:477-87. [PMID: 26040315 DOI: 10.1093/abbs/gmv041] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 02/11/2015] [Indexed: 12/18/2022] Open
Abstract
Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.
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Affiliation(s)
- Guang-Zhe Ge
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Tian-Rui Xu
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
| | - Ceshi Chen
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
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14
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Wu ZJ, Li XH, Liu ZW, Xu ZS, Zhuang J. De novo assembly and transcriptome characterization: novel insights into catechins biosynthesis in Camellia sinensis. BMC PLANT BIOLOGY 2014; 14:277. [PMID: 25316555 PMCID: PMC4203915 DOI: 10.1186/s12870-014-0277-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 10/06/2014] [Indexed: 05/18/2023]
Abstract
BACKGROUND Tea is a popular natural non-alcoholic beverage consumed worldwide due to its bioactive ingredients, particularly catechins (flavan-3-ols). Catechins not only contribute to tea quality but also serve important functions in the anti-stress regulation of secondary metabolic pathways. However, the percentages of various catechins are different among tea plant [Camellia sinensis (L.) O. Kuntze] cultivars. This study aimed to elucidate the biosynthetic mechanism of catechins. Transcriptomes from leaf tissues of four tea plant cultivars, 'Yunnanshilixiang', 'Chawansanhao', 'Ruchengmaoyecha', and 'Anjibaicha', were sequenced using the high-throughput sequencing platform Illumina HiSeq™ 2000. De novo assemble were also performed. Catechins contents were measured through reversed-phase high-performance liquid chromatography (RP-HPLC), and the biosynthetic pathway was also surveyed. RESULTS We constructed a unified unigene database. A total of 146,342 pairs of putative orthologs from the four tea plant cultivars, 'Yunnanshilixiang', 'Chawansanhao', 'Ruchengmaoyecha', and 'Anjibaicha' were generated. Approximately 68,890 unigenes (47.1%) were aligned to the sequences of seven public databases with a cut-off E-value of 1E-5. A total of 217 differentially expressed genes were found through RPKM values, and 150 unigenes were assigned to the flavonoid biosynthetic pathway using the integrated function annotation. The (-)-EGC and (-)-EC contents were significantly lower and the (+)-GC and (+)-C contents were abnormally higher in 'Ruchengmaoyecha' than in 'Yunnanshilixiang', 'Chawansanhao', and 'Anjibaicha'. The proportion of catechins was confirmed by selecting critical genes (ANS, ANR, and LAR) for qRT-PCR analysis. CONCLUSIONS This study provided a global survey of transcriptomes from four tea plant cultivars and serves as an available resource of genetic diversity. The analyses of transcriptome profiles and physiological indicators not only identified the putative genes involved in the flavonoid biosynthetic pathway but also provided some novel insights for the mechanisms of catechins biosynthesis.
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Affiliation(s)
- Zhi-Jun Wu
- />Tea Science Research Institute, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095 China
| | - Xing-Hui Li
- />Tea Science Research Institute, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095 China
| | - Zhi-Wei Liu
- />Tea Science Research Institute, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095 China
| | - Zhi-Sheng Xu
- />State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095 China
| | - Jing Zhuang
- />Tea Science Research Institute, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095 China
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Lambert JD. Does tea prevent cancer? Evidence from laboratory and human intervention studies. Am J Clin Nutr 2013; 98:1667S-1675S. [PMID: 24172300 DOI: 10.3945/ajcn.113.059352] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Tea (Camellia sinensis) is a widely consumed beverage and has been extensively studied for its cancer-preventive activity. Both the polyphenolic constituents as well as the caffeine in tea have been implicated as potential cancer-preventive compounds; the relative importance seems to depend on the cancer type. Green tea and the green tea catechin have been shown to inhibit tumorigenesis at a number of organ sites and to be effective when administered either during the initiation or postinitiation phases of carcinogenesis. Black tea, although not as well studied as green tea, has also shown cancer-preventive effects in laboratory models. A number of potential mechanisms have been proposed to account for the cancer-preventive effects of tea, including modulation of phase II metabolism, alterations in redox environment, inhibition of growth factor signaling, and others. In addition to the laboratory studies, there is a growing body of human intervention studies suggesting that tea can slow cancer progression and modify biomarkers relevant to carcinogenesis. Although available data are promising, many questions remain with regard to the dose-response relations of tea constituents in various models, the primary mechanisms of action, and the potential for combination chemoprevention strategies that involve tea as well as other dietary or pharmaceutical agents. The present review examines the available data from laboratory animal and human intervention studies on tea and cancer prevention. These data were evaluated, and areas for further research are identified.
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Affiliation(s)
- Joshua D Lambert
- Center of Excellence for Plant and Mushroom Foods for Health, the Department of Food Science, Pennsylvania State University, University Park, PA
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Sun S, Pan S, Miao A, Ling C, Pang S, Tang J, Chen D, Zhao C. Active extracts of black tea (Camellia Sinensis) induce apoptosis of PC-3 prostate cancer cells via mitochondrial dysfunction. Oncol Rep 2013; 30:763-72. [PMID: 23715786 DOI: 10.3892/or.2013.2504] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Accepted: 05/07/2013] [Indexed: 11/06/2022] Open
Abstract
Cancer of the prostate gland is the most common invasive malignancy and the second leading cause of cancer-related death in human males. Many studies have shown that black tea reduces the risk of several types of cancer. We studied the effects of active extracts of black tea and the black tea polyphenols theaflavins (TFs), on the cellular proliferation and mitochondria of the human prostate cancer cell line PC-3. Our studies revealed that Yinghong black tea extracts (YBT), Assam black tea extracts (ABT) and TFs inhibited cell proliferation in a dose-dependent manner. We also showed that TFs, YBT and ABT affected the morphology of PC-3 cells and induced apoptosis or even necrosis in PC-3 cells. In addition, it was observed that the samples significantly caused loss of the mitochondrial membrane potential, release of cytochrome c from the intermembrane space into the cytosol, decrease of the ATP content and activation of caspase-3 compared with the control. Taken together, these findings suggest that black tea could act as an effective anti-proliferative agent in PC-3 cells, and TFs, YBT and ABT induced apoptosis of PC-3 cells through mitochondrial dysfunction.
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Affiliation(s)
- Shili Sun
- Drink Plant Research Institute/Tea Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou, Guangdong 510640, PR China
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Black tea in chemo-prevention of cancer and other human diseases. FOOD SCIENCE AND HUMAN WELLNESS 2013. [DOI: 10.1016/j.fshw.2013.03.004] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Chen H, Shurlknight K, Leung T, Sang S. Structural identification of theaflavin trigallate and tetragallate from black tea using liquid chromatography/electrospray ionization tandem mass spectrometry. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:10850-10857. [PMID: 23066878 DOI: 10.1021/jf303749z] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Black tea contains two major pigments, theaflavins and thearubigins. These polyphenols have been associated with certain health benefits including prevention of heart disease and cancer. Elucidating and characterizing the structural aspects of thearubigins, the most abundant pigment in black tea, has been a challenge for many years. Therefore further studies of black tea polyphenols must be conducted in effort to solve this thearubigin dispute. In the present study, black tea extract was found to possess theaflavin trigallate and tetragallate by means of liquid chromatography/electrospray ionization mass spectrometry. These structures were confirmed by analysis of the MS(n) (n = 1-4) spectra and comparison of the MS/MS spectra of the product ions to the MS/MS spectra of authentic (-)-epigallocatechin-3-gallate, (-)-epicatechin-3-gallate and theaflavin-3,3'-digallate. To our knowledge, this is the first report to confirm the presence of theaflavin trigallate and tetragallate in black tea.
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Affiliation(s)
- Huadong Chen
- Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA
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Weisburger JH. Prevention of coronary heart disease and cancer by tea, a review. Environ Health Prev Med 2012; 7:283-8. [PMID: 21432397 DOI: 10.1007/bf02908887] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2002] [Accepted: 11/14/2002] [Indexed: 12/31/2022] Open
Abstract
Biomedical research has uncovered the mechanisms whereby tea promotes good health and lowers the risk of major chronic diseases, such as heart disease and many types of cancer. The active components in tea are polyphenols, epigallocatechin gallate in green tea, theaflavins and thearubigins in black tea. Green and black tea and the polyphenols have similar beneficial effects. The mechanisms are categorized into 5 groups. 1) Tea polyphenols are powerful antioxidants. They decrease the oxidation of LDL cholesterol and lower the risk of heart disease, and also inhibit action of reactive oxygen species mediating the oxidation of DNA associated with carcinogenesis 2) Tea polyphenols induce detoxifying enzymes, glucuronosyl transferases, eliminating active forms of carcinogens and other toxicants, accounting for the lower cancer risk. 3) Tea polyphenols lower duplication rates of cancer cells and inhibit the growth of cancer, increase apoptosis and lower angiogenesis. 4) Tea polyphenols alter the intestinal bacterial flora, suppressing undesirable bacteria and favoring growth of beneficial bacteria. 5) Aging phenomena, and diseases associated with the formation of reactive oxygen species (ROS) are inhibited.
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Affiliation(s)
- John H Weisburger
- Institute for Cancer Prevention, American Health Foundation, 1 Dana Road, 10595, Valhalla, NY, USA,
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Das L, Bhaumik E, Raychaudhuri U, Chakraborty R. Role of nutraceuticals in human health. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2012; 49:173-83. [PMID: 23572839 PMCID: PMC3550857 DOI: 10.1007/s13197-011-0269-4] [Citation(s) in RCA: 226] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 04/14/2010] [Accepted: 07/06/2010] [Indexed: 12/25/2022]
Abstract
Nutraceutical is the hybrid of 'nutrition' and 'pharmaceutical'. Nutraceuticals, in broad, are food or part of food playing a significant role in modifying and maintaining normal physiological function that maintains healthy human beings. The principal reasons for the growth of the nutraceutical market worldwide are the current population and the health trends. The food products used as nutraceuticals can be categorized as dietary fibre, prebiotics, probiotics, polyunsaturated fatty acids, antioxidants and other different types of herbal/ natural foods. These nutraceuticals help in combating some of the major health problems of the century such as obesity, cardiovascular diseases, cancer, osteoporosis, arthritis, diabetes, cholesterol etc. In whole, 'nutraceutical' has lead to the new era of medicine and health, in which the food industry has become a research oriented sector.
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Affiliation(s)
- Lipi Das
- Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, 700032 India
| | - Eshani Bhaumik
- Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, 700032 India
| | - Utpal Raychaudhuri
- Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, 700032 India
| | - Runu Chakraborty
- Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, 700032 India
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Chen H, Parks TA, Chen X, Gillitt ND, Jobin C, Sang S. Structural identification of mouse fecal metabolites of theaflavin 3,3'-digallate using liquid chromatography tandem mass spectrometry. J Chromatogr A 2011; 1218:7297-7306. [PMID: 21906744 PMCID: PMC3376406 DOI: 10.1016/j.chroma.2011.08.056] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Revised: 08/06/2011] [Accepted: 08/12/2011] [Indexed: 12/01/2022]
Abstract
Black tea consumption has been associated with many health benefits including the prevention of cancer and heart disease. Theaflavins are the major bioactive polyphenols present in black tea. Unfortunately, limited information is available on their biotransformation. In the present study, we investigated the metabolic fate of theaflavin 3,3'-digallate (TFDG), one of the most abundant and bioactive theaflavins, in mouse fecal samples using liquid chromatography/electrospray ionization tandem mass spectrometry by analyzing the MS(n) (n=1-3) spectra. Four metabolites theaflavin, theaflavin 3-gallate, theaflavin 3'-gallate, and gallic acid were identified as the major mouse fecal metabolites of TFDG. Glucuronidated and sulfated, instead of methylated metabolites of theaflavin 3-gallate, theaflavin 3'-gallate, and TFDG were detected and identified as the minor mouse fecal metabolites of TFDG. Our results indicate that TFDG can be degraded in mice. Further studies on the formation of those metabolites in TFDG-treated mice in germ-free conditions are warranted. To our knowledge, this is the first report on the biotransformation of TFDG in mice.
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Affiliation(s)
- Huadong Chen
- Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA
| | - Tiffany A. Parks
- Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA
| | - Xiaoxin Chen
- Cancer Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, USA
| | - Nicholas D. Gillitt
- Dole Nutrition Research Laboratory, North Carolina Research Campus, 600 Laureate Way, Kannapolis, NC 28081, USA
| | - Christian Jobin
- Department of Medicine, Pharmacology and Immunology/Microbiology and the Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Shengmin Sang
- Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA
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Bhattacharya U, Mukhopadhyay S, Giri AK. Comparative antimutagenic and anticancer activity of three fractions of black tea polyphenols thearubigins. Nutr Cancer 2011; 63:1122-32. [PMID: 21919645 DOI: 10.1080/01635581.2011.605985] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Antimutagenic and anticancer effects of black tea polyphenols theaflavins (TF) and thearubigins (TR) have previously been reported. TR is a complex mixture of polyphenols. In this study, our interest was to fractionate TR and to study the antimutagenic and anticancer activities of the fractions. Three fractions of TR, namely TR-1, TR-2, and TR-3, were isolated by chromatographic processes. Antimutagenic activity of these 3 fractions was carried out on 4 Salmonella strains by Ames assay. Anticancer activity was studied on human leukemic cells U937. Our findings clearly indicated antimutagenic and anticancer activities of the TR-1, TR-2, and TR-3 fractions on Salmonella strains and on U937 cells, respectively. However, all 3 fractions, at or below 100 μg/ml dose, did not show any significant toxic effects on the normal human cells (peripheral blood mononuclear cells). TR-2 was found to be the most active fraction among the 3. Flow cytometric and confocal microscopic studies further indicate that apoptosis induction could be an important mechanism behind the anticancer effects of these fractions. To our knowledge, this study is the first attempt to describe the antimutagenic and anticancer activity of TR fractions, and it also suggests that TR-2 is the most active component of TR.
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Affiliation(s)
- Udayan Bhattacharya
- Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India
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23
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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: 77] [Impact Index Per Article: 5.5] [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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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: 169] [Impact Index Per Article: 12.1] [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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Chakrabarty S, Das A, Bhattacharya A, Chakrabarti G. Theaflavins depolymerize microtubule network through tubulin binding and cause apoptosis of cervical carcinoma HeLa cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:2040-2048. [PMID: 21323312 DOI: 10.1021/jf104231b] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Here we studied the antiproliferative activity of theaflavins in cervical carcinoma HeLa cells by investigating their effects on cellular microtubules and purified goat brain tubulin. Theaflavins inhibited proliferation of HeLa cells with IC(50) value of 110 ± 2.1 μg/mL (p = < 0.01), caused cell cycle arrest at G(2)/M phase and induced apoptosis with alteration of expression of pro- and antiapoptotic proteins. Along with these antiproliferative activities, theaflavins act as microtubule depolymerizers. Theaflavins disrupted the microtubule network accompanied by alteration of cellular morphology and also decreased the polymeric tubulin mass of the cells. The polymerization of cold treated depolymerized microtubules in HeLa cells was prevented in the presence of theaflavins. In vitro polymerization of purified tubulin into microtubules was also inhibited by theaflavins with an IC(50) value of 78 ± 2.43 μg/mL (P < 0.01). Thus, disruption of cellular microtubule network of HeLa cells through microtubule depolymerization may be one of the possible mechanisms of antiproliferative activity of theaflavins.
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Affiliation(s)
- Subhendu Chakrabarty
- Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India
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Abstract
The incidence of nonmelanoma skin cancer is increasing every year. Basal cell carcinoma and squamous cell carcinoma are the two major types of nonmelanoma skin cancer. Among other factors, understanding the potential role of nutrients in the development, progression, and treatment of nonmelanoma skin cancer is critical. This contribution provides a review of the nutrients that have been more extensively investigated in the literature with regard to nonmelanoma skin cancer, including dietary fats, retinol, carotenoids, vitamin C, vitamin D, vitamin E, selenium, copper, iron, zinc, green tea, and black tea.
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Affiliation(s)
- Michael J Payette
- Department of Dermatology, MC-6230, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
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Abstract
Extracts of green tea and green tea polyphenols have exhibited inhibitory effects against the formation and development of tumors at different organ sites in animals. These include animal models for skin, lung, oral cavity, esophagus, stomach, intestine, colon, liver, pancreas, bladder, mammary gland, and prostate cancers. In addition to suppressing cell proliferation, promoting apoptosis, and modulating signaling transduction, green tea polyphenols, especially (-)-epigallocatechin-3-gallate, also inhibit cell invasion, angiogenesis, and metastasis. This article reviews data on the cancer preventive activities of green tea polyphenols, possible mechanisms involved, and the relationship between green tea consumption and human cancer risk.
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Affiliation(s)
- Chung S Yang
- Department of Chemical Biology, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854-8020, USA.
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SMARSH DN, LIBURT N, STRELTSOVA J, McKEEVER K, WILLIAMS CA. Oxidative stress and antioxidant status in intensely exercising horses administered nutraceutical extracts. Equine Vet J 2010:317-22. [DOI: 10.1111/j.2042-3306.2010.00182.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Flavonoids in Cancer Prevention and Therapy: Chemistry, Pharmacology, Mechanisms of Action, and Perspectives for Cancer Drug Discovery. ALTERNATIVE AND COMPLEMENTARY THERAPIES FOR CANCER 2010. [PMCID: PMC7120123 DOI: 10.1007/978-1-4419-0020-3_23] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Among the numerous products available from plants, the flavonoid superfamily plays a central role by its large number of molecules (over 6000) and also by the role these products occupy in the normal physiology of plants. Flavonoids are secondary plant metabolites involved in several biological processes (e.g., germination, UV protection, insecticides) and are also involved in the attraction of pollinating agents via the vivid colors of the anthocyanin pigments found in flowers (e.g., blue, purple, yellow, orange, and red) [1–3]. Flavonoids are found in the normal human diet composed of green vegetables, onions, fruits (apples, grapes, strawberries, etc.), beverages (coffee, tea, beer, red wine) [4, 5], and isoflavonoids are mainly found in soya bean-derived products [6].
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Faria A, Pestana D, Teixeira D, Azevedo J, De Freitas V, Mateus N, Calhau C. Flavonoid transport across RBE4 cells: A blood-brain barrier model. Cell Mol Biol Lett 2010; 15:234-41. [PMID: 20140760 PMCID: PMC6275689 DOI: 10.2478/s11658-010-0006-4] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2009] [Accepted: 02/02/2010] [Indexed: 12/12/2022] Open
Abstract
There is a growing interest in dietary therapeutic strategies to combat oxidative stress-induced damage to the Central Nervous System (CNS), which is associated with a number of pathophysiological processes, including Alzheimer's and Parkinson's diseases and cerebrovascular diseases. Identifying the mechanisms associated with phenolic neuroprotection has been delayed by the lack of information concerning the ability of these compounds to enter the CNS. The aim of this study was to evaluate the transmembrane transport of flavonoids across RBE-4 cells (an immortalized cell line of rat cerebral capillary endothelial cells) and the effect of ethanol on this transport. The detection and quantification of all of the phenolic compounds in the studied samples (basolateral media) was performed using a HPLC-DAD (Diode Array Detector). All of the tested flavonoids (catechin, quercetin and cyanidin-3-glucoside) passed across the RBE-4 cells in a time-dependent manner. This transport was not influenced by the presence of 0.1% ethanol. In conclusion, the tested flavonoids were capable of crossing this blood-brain barrier model.
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Affiliation(s)
- Ana Faria
- Department of Biochemistry, University of Porto, Portugal.
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Bhattacharya U, Halder B, Mukhopadhyay S, Giri AK. Role of oxidation-triggered activation of JNK and p38 MAPK in black tea polyphenols induced apoptotic death of A375 cells. Cancer Sci 2009; 100:1971-8. [PMID: 19594545 PMCID: PMC11158723 DOI: 10.1111/j.1349-7006.2009.01251.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Theaflavins (TF) and thearubigins (TR) are the major polyphenols of black tea. Our previous study revealed that TF- and TR-induced apoptosis of human malignant melanoma cells (A375) is executed via a mitochondria-mediated pathway. In our present study we observed the role of the three most important MAPK (ERK, JNK, and p38) in TF- and TR-induced apoptosis. TF and TR treatment of A375 cells led to sustained activation of JNK and p38 MAPK but not ERK, suggesting that JNK and p38 are the effector molecules in this polyphenol-induced cell death. This idea was further supported by subsequent studies in which JNK and p38 activation was inhibited by specific inhibitors. Significant inhibition was found in TF- and TR-treated A375 cell death pretreated with JNK- or p38-specific inhibitors only. Further, we have found that TF and TR treatment induces a time-dependent increase in intracellular reactive oxygen species generation in A375 cells. Interestingly, treatment with the antioxidant N-acetyl cystein inhibits TF- and TR-induced JNK and p38 activation as well as induction of cell death in A375 cells. We also provide evidence demonstrating the critical role of apoptosis signal-regulating kinase 1 in TF- and TR-induced apoptosis in A375 cells. Taken together our results strongly suggest that TF and TR induce apoptotic death of A375 cells through apoptosis signal-regulating kinase 1, MAPK kinase, and the JNK-p38 cascade, which is triggered by N-acetyl cystein intracellular oxidative stress.
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Affiliation(s)
- Udayan Bhattacharya
- Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India
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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: 826] [Impact Index Per Article: 51.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [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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Abstract
Tea is the most widely used ancient beverage in the world and black tea possesses many biological effects on the organisms. It acts as an effective antioxidant because of its free radical-scavenging and metal-chelating ability. Due to this, it is active against inflammation, clastogenesis, and several types of cancer. Tea reduces DNA damage and mutagenesis due to oxidative stress or the presence of pro-mutagens through antioxidant function, blocking activation pathways of mutagens, suppressing transcription of enzymes involved etc. Inhibition of low-density lipoprotein (LDL) peroxidation, suppression of fatty acid synthase etc., suggest that tea may have a role in preventing cardiovascular diseases. Some epidemiological studies support the protective role of black tea against cardiovascular diseases but some do not. Besides, black tea has beneficial effects on the gastrointestinal tract; it affects motility, absorption, microflora etc., by influencing the hormonal balance and antioxidant function black tea improves bone mineral density. It is also antiviral due to its enzyme-inhibiting and receptor-blocking properties. Although its role in cancers of the gastrointestinal tract, liver, and prostate is confirmed, its effect against urinary tract cancer is uncertain and further studies are required. Apart from these, excess consumption may lead to the formation of a stained pellicle layer on teeth, which is difficult to eliminate, inhibits trypsin, influences mineral absorption, causes convulsions etc. Excess caffeine intake may have adverse effects on selected organs as reported in studies on some organisms. These reports indicate that there is a wide scope of further research for the efficient use of black tea active conserves/isolates to reap health benefits.
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Affiliation(s)
- Vasundhara Sharma
- Plantation Products, Spices and Flavour Technology Department, Central Food Technological Research Institute, Mysore, India
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Manna S, Mukherjee S, Roy A, Das S, Panda CK. Tea polyphenols can restrict benzo[a]pyrene-induced lung carcinogenesis by altered expression of p53-associated genes and H-ras, c-myc and cyclin D1. J Nutr Biochem 2009; 20:337-49. [DOI: 10.1016/j.jnutbio.2008.04.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2007] [Revised: 03/17/2008] [Accepted: 04/01/2008] [Indexed: 12/23/2022]
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Yang CS, Lambert JD, Sang S. Antioxidative and anti-carcinogenic activities of tea polyphenols. Arch Toxicol 2009; 83:11-21. [PMID: 19002670 PMCID: PMC2820244 DOI: 10.1007/s00204-008-0372-0] [Citation(s) in RCA: 213] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2008] [Accepted: 10/02/2008] [Indexed: 10/21/2022]
Abstract
Tea (Camellia sinensis, Theaceace), a popular beverage consumed world-wide, has been studied for its preventive effects against cancer as well as cardiovascular, neurodegenerative, and other diseases. Most of the proposed beneficial effects have been attributed to the polyphenolic compounds in tea, but the nature of these activities and the molecular mechanisms of their actions remain unclear. Tea polyphenols are known to be strong antioxidants. Prevention of oxidative stress, modulation of carcinogen metabolism, and prevention of DNA damage have been suggested as possible cancer preventive mechanisms for tea and tea polyphenols. In this chapter, we discuss these topics in the light of biotransformation and bioavailability of tea polyphenols. We also review the preventive effects of tea polyphenols in animal models of carcinogenesis and some of the possible post-initiation mechanisms of action. Finally, we discuss the effects of tea consumption on cancer risk in humans. It is our aim to raise some of the unanswered questions regarding cancer prevention by tea and to stimulate further research in this area.
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Affiliation(s)
- Chung S Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, 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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37
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Lu G, Xiao H, You H, Lin Y, Jin H, Snagaski B, Yang CS. Synergistic Inhibition of Lung Tumorigenesis by a Combination of Green Tea Polyphenols and Atorvastatin. Clin Cancer Res 2008; 14:4981-8. [DOI: 10.1158/1078-0432.ccr-07-1860] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Yokohira M, Takeuchi H, Saoo K, Matsuda Y, Yamakawa K, Hosokawa K, Kuno T, Imaida K. Establishment of a bioassay model for lung cancer chemoprevention initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice. ACTA ACUST UNITED AC 2008; 60:469-73. [PMID: 18639446 DOI: 10.1016/j.etp.2008.05.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2008] [Revised: 05/20/2008] [Accepted: 05/21/2008] [Indexed: 10/21/2022]
Abstract
AIMS In order to prevent lung cancer development in people at high risk, identification of chemopreventive agents may be important. The present study was conducted to establish a bioassay model for this purpose. In particular, the time course of 4-(methylnitrosamno)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor development was examined to determine the most appropriate shortest period to assess effects of test agents, with 8-methoxypsoralen (8-MOP) as a typical example. METHODS A total of 124 mice were separated into two groups (Group A: 60 mice, Group B: 64 mice), pretreated with 100ppm 8-MOP (Group A) or basal diet (Group B) for 3 days before receiving single doses of NNK (2mg/0.1ml saline/mouse i.p.) on days 0 and 7. Subgroups of 15 mice of each group were then sacrificed after 8, 10, 12, and 16 weeks. RESULTS Microscopically, the earliest time point when significant differences in data for hyperplasia, adenoma and hyperplasia and adenoma could be detected was 12 weeks. A trend was noted for 8-MOP to reduce adenomas to a greater extent than hyperplasia. DISCUSSION In conclusion, the results of this study showed that the double i.p. treatment with NNK and 12 weeks duration are effective for detection of lung cancer chemoprevention in our A/J mouse lung tumorigenesis model.
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Affiliation(s)
- Masanao Yokohira
- Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
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Singh M, Arseneault M, Sanderson T, Murthy V, Ramassamy C. Challenges for research on polyphenols from foods in Alzheimer's disease: bioavailability, metabolism, and cellular and molecular mechanisms. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2008; 56:4855-73. [PMID: 18557624 DOI: 10.1021/jf0735073] [Citation(s) in RCA: 266] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Polyphenols are the most abundant antioxidants in diet. Indeed, fruits, vegetables, beverages (tea, wine, juices), plants, and some herbs are loaded with powerful antioxidant polyphenols. Despite their wide distribution, research on human health benefits truly began in the mid-1990s (Scalbert, A.; Johnson, I. T.; Saltmarsh, M. Am. J. Clin. Nutr. 2005, 81, S15S-217S). Phenolic compounds have been receiving increasing interest from consumers and manufacturers because numerous epidemiological studies have suggested associations between consumption of polyphenol-rich foods or beverages and the prevention of certain chronic diseases such as cancers and cardiovascular diseases (Manach, C.; Mazur, A.; Scalbert, A. Curr. Opin. Lipidol. 2005, 16, 77-84; Duthie, S. J. Mol. Nutr. Food Res. 2007, 51, 665-674). Furthermore, in the past 10 years, research on the neuroprotective effects of dietary polyphenols has developed considerably. These compounds are able to protect neuronal cells in various in vivo and in vitro models through different intracellular targets (Ramassamy, C. Eur. J. Pharmacol. 2006, 545, 51-64). However, it is not at all clear whether these compounds reach the brain in sufficient concentrations and in a biologically active form to exert beneficial effects. On the other hand, it has become clear that the mechanisms of action of these polyphenols go beyond their antioxidant activity and the attenuation of oxidative stress. Therefore, there is a need for more research on their intracellular and molecular targets as special pathways underlying distinct polyphenol-induced neuroprotection. The focus of this review is aimed at presenting the role of some polyphenols from fruits, vegetables, and beverages in neuroprotection and particularly in Alzheimer's disease and the research challenges in this area.
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Affiliation(s)
- Manjeet Singh
- INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, Québec H7V 1B7, Canada
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40
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Ju J, Lu G, Lambert JD, Yang CS. Inhibition of carcinogenesis by tea constituents. Semin Cancer Biol 2007; 17:395-402. [PMID: 17686632 PMCID: PMC2736048 DOI: 10.1016/j.semcancer.2007.06.013] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2007] [Revised: 06/21/2007] [Accepted: 06/27/2007] [Indexed: 10/23/2022]
Abstract
The possible cancer preventive activity of tea has received much attention in recent years. The inhibitory activities of tea and tea constituents against carcinogenesis at different organ sites have been demonstrated in many animal models. The effect of tea consumption on human cancers, however, remains inconclusive. The mechanisms of action of tea polyphenols, especially EGCG, the most abundant and active catechin, have been extensively investigated. Most of the studies, however, were based on cell culture systems, and 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. Human intervention trials are warranted to determine the possible prevention of cancer of specific sites by preparation of tea constituents.
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Affiliation(s)
- Jihyeung Ju
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
| | - Gang Lu
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
| | - Joshua D. Lambert
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
| | - Chung S. Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
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41
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Lu G, Liao J, Yang G, Reuhl KR, Hao X, Yang CS. Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Res 2007; 66:11494-501. [PMID: 17145898 DOI: 10.1158/0008-5472.can-06-1497] [Citation(s) in RCA: 113] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.
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Affiliation(s)
- Gang Lu
- Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 16445-0687, USA
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Weng MS, Ho CT, Ho YS, Lin JK. Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling. Toxicol Appl Pharmacol 2007; 218:107-18. [PMID: 17182072 DOI: 10.1016/j.taap.2006.10.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2006] [Revised: 09/28/2006] [Accepted: 10/24/2006] [Indexed: 11/30/2022]
Abstract
Fatty acid synthase (FAS) is a major lipogenic enzyme catalyzing the synthesis of long-chain saturated fatty acids. Most breast cancers require lipogenesis for growth. Here, we demonstrated the effects of theanaphthoquinone (TNQ), a member of the thearubigins generated by the oxidation of theaflavin (TF-1), on the expression of FAS in human breast cancer cells. TNQ was found to suppress the EGF-induced expression of FAS mRNA and FAS protein in MDA-MB-231 cells. Expression of FAS has previously been shown to be regulated by the SREBP family of transcription factors. In this study, we demonstrated that the EGF-induced nuclear translocation of SREBP-1 was blocked by TNQ. Moreover, TNQ also modulated EGF-induced ERK1/2 and Akt phosphorylation. Treatment of MDA-MB-231 cells with PI 3-kinase inhibitors, LY294002 and Wortmannin, inhibited the EGF-induced expression of FAS and nuclear translocation of SREBP-1. Treatment with TNQ inhibited EGF-induced EGFR/ErbB-2 phosphorylation and dimerization. Furthermore, treatment with kinase inhibitors of EGFR and ErbB-2 suggested that EGFR/ErbB-2 activation was involved in EGF-induced FAS expression. In constitutive FAS expression, TNQ inhibited FAS expression and Akt autophosphorylation in BT-474 cells. The PI 3-kinase inhibitors and tyrosine kinase inhibitors of EGFR and ErbB-2 also reduced constitutive FAS expression. In addition, pharmacological blockade of FAS by TNQ decreased cell viability and induced cell death in BT-474 cells. In summary, our findings suggest that TNQ modulates FAS expression by the regulation of EGFR/ErbB-2 pathways and induces cell death in breast cancer cells.
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Affiliation(s)
- Meng-Shih Weng
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 10018, Taiwan
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Slivova V, Zaloga G, DeMichele SJ, Mukerji P, Huang YS, Siddiqui R, Harvey K, Valachovicova T, Sliva D. Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells. Nutr Cancer 2006; 52:66-73. [PMID: 16091006 DOI: 10.1207/s15327914nc5201_9] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Many epidemiological studies have suggested that consumption of green tea may decrease the risk of cancer. The chemopreventive effect of green tea polyphenols (GTP) has been demonstrated through the inhibition of cell proliferation and angiogenesis in cell culture and animal models of breast cancer. Metastasis of breast cancer is the major reason for the high mortality of breast cancer patients and is directly linked to the invasive behavior of breast cancer cells. Cancer metastasis consists of several interdependent processes including cancer cell adhesion, cancer cell migration, and invasion of cancer cells. In this study, we evaluated the effect of GTP on human breast cancer cells, and we show that in addition to inhibiting cell growth, GTP also suppressed the invasive behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result of the inhibition of constitutively active transcription factors AP-1 and NF-kappaB, which further suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Based on these results, it can be hypothesized that GTP treatment resulted in the inhibition of formation of signaling complexes responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin, integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate that GTP may contribute to the anticancer effects of green tea by inhibiting the invasive behavior of cancer cells.
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Affiliation(s)
- Veronika Slivova
- Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA
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Galati G, Lin A, Sultan AM, O'Brien PJ. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med 2006; 40:570-80. [PMID: 16458187 DOI: 10.1016/j.freeradbiomed.2005.09.014] [Citation(s) in RCA: 261] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2005] [Revised: 08/23/2005] [Accepted: 09/08/2005] [Indexed: 02/07/2023]
Abstract
Tea phenolic acids and catechins containing gallic acid moieties are most abundant in green tea, and various medical benefits have been proposed from their consumption. In the following, the cytotoxicities of these major tea phenolics toward isolated rat hepatocytes have been ranked and the mechanisms of cytotoxicity evaluated. The order of cytotoxic effectiveness found was epigallocatechin-3-gallate>propyl gallate>epicatechin-3-gallate>gallic acid, epigallocatechin>epicatechin. Using gallic acid as a model tea phenolic and comparing it with the tea catechins and gallic acid-derivative food supplements, the major cytotoxic mechanism found with hepatocytes was mitochondrial membrane potential collapse and ROS formation. Epigallocatechin-3-gallate was also the most effective at collapsing the mitochondrial membrane potential and inducing ROS formation. Liver injury was also observed in vivo when these tea phenolics were administered ip to mice, as plasma alanine aminotransferase levels were significantly increased. In contrast, GSH conjugation, methylation, metabolism by NAD(P)H:quinone oxidoreductase 1, and formation of an iron complex were important in detoxifying the gallic acid. In addition, for the first time, the GSH conjugates of gallic acid and epigallocatechin-3-gallate have been identified using mass spectrometry. These results add insight into the cytotoxic and cytoprotective mechanisms of the simple tea phenolic acids and the more complex tea catechins.
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Affiliation(s)
- Giuseppe Galati
- Department of Pharmacology, University of Toronto, Toronto, ON, Canada
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45
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Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 2005; 20:187-210. [PMID: 16289744 DOI: 10.1016/j.tiv.2005.06.048] [Citation(s) in RCA: 583] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2004] [Revised: 04/01/2005] [Accepted: 06/01/2005] [Indexed: 02/08/2023]
Abstract
Flavonoids are present in fruits, vegetables and beverages derived from plants (tea, red wine), and in many dietary supplements or herbal remedies including Ginkgo Biloba, Soy Isoflavones, and Milk Thistle. Flavonoids have been described as health-promoting, disease-preventing dietary supplements, and have activity as cancer preventive agents. Additionally, they are extremely safe and associated with low toxicity, making them excellent candidates for chemopreventive agents. The cancer protective effects of flavonoids have been attributed to a wide variety of mechanisms, including modulating enzyme activities resulting in the decreased carcinogenicity of xenobiotics. This review focuses on the flavonoid effects on cytochrome P450 (CYP) enzymes involved in the activation of procarcinogens and phase II enzymes, largely responsible for the detoxification of carcinogens. A number of naturally occurring flavonoids have been shown to modulate the CYP450 system, including the induction of specific CYP isozymes, and the activation or inhibition of these enzymes. Some flavonoids alter CYPs through binding to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, acting as either AhR agonists or antagonists. Inhibition of CYP enzymes, including CYP 1A1, 1A2, 2E1 and 3A4 by competitive or mechanism-based mechanisms also occurs. Flavones (chrysin, baicalein, and galangin), flavanones (naringenin) and isoflavones (genistein, biochanin A) inhibit the activity of aromatase (CYP19), thus decreasing estrogen biosynthesis and producing antiestrogenic effects, important in breast and prostate cancers. Activation of phase II detoxifying enzymes, such as UDP-glucuronyl transferase, glutathione S-transferase, and quinone reductase by flavonoids results in the detoxification of carcinogens and represents one mechanism of their anticarcinogenic effects. A number of flavonoids including fisetin, galangin, quercetin, kaempferol, and genistein represent potent non-competitive inhibitors of sulfotransferase 1A1 (or P-PST); this may represent an important mechanism for the chemoprevention of sulfation-induced carcinogenesis. Importantly, the effects of flavonoids on enzymes are generally dependent on the concentrations of flavonoids present, and the different flavonoids ingested. Due to the low oral bioavailability of many flavonoids, the concentrations achieved in vivo following dietary administration tend to be low, and may not reflect the concentrations tested under in vitro conditions; however, this may not be true following the ingestion of herbal preparations when much higher plasma concentrations may be obtained. Effects will also vary with the tissue distribution of enzymes, and with the species used in testing since differences between species in enzyme activities also can be substantial. Additionally, in humans, marked interindividual variability in drug-metabolizing enzymes occurs as a result of genetic and environmental factors. This variability in xenobiotic metabolizing enzymes and the effect of flavonoid ingestion on enzyme expression and activity can contribute to the varying susceptibility different individuals have to diseases such as cancer. As well, flavonoids may also interact with chemotherapeutic drugs used in cancer treatment through the induction or inhibition of their metabolism.
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Affiliation(s)
- Young Jin Moon
- Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260-1200, USA
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Banerjee S, Manna S, Saha P, Panda CK, Das S. Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo(a)pyrene-induced lung carcinogenesis. Eur J Cancer Prev 2005; 14:215-21. [PMID: 15901989 DOI: 10.1097/00008469-200506000-00004] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
One of the most promising strategies for cancer prevention is chemoprevention by daily used food and beverages. Black tea, the most widely consumed beverage, is a source of compounds with antioxidative, antimicrobial, antimutagenic and anticarcinogenic properties. Lung cancer is the most common cause of cancer deaths in both men and women worldwide. Over one million people around the world are likely to be killed by lung cancer due to increased tobacco smoking and environmental pollutants, especially car exhausts. Therefore chemopreventive intervention using black tea and its active components may be a viable means to reduce lung cancer death. In the present investigation, we used benzo(a)pyrene (BP) to induce lung carcinogenesis in mice for the assessment of potential apoptosis-inducing and proliferation-suppressing effects of theaflavins and epigallocatechin gallate, active components of black tea. Hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks respectively, were effectively reduced after treatment with theaflavins and epigallocatechin gallate. Significant reduction in number of proliferating cells and increased number of apoptotic cells was also found on the 8th, 17th and 26th week of treatment with theaflavins and epigallocatechin gallate in BP-exposed mice. Our observation suggests a promising role for black tea polyphenols in the prevention of lung cancer.
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Affiliation(s)
- S Banerjee
- Department of Cancer Chemoprevention, Chittarajan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, West Bengal, 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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Abstract
Tea and tea constituents have been shown by different investigators to inhibit lung tumorigenesis in different animal model systems. This includes lung tumorigenesis in A/J mice induced by 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK), N-nitrosodiethylamine, benzo[a]pyrene, N-nitrosomethylurea, or cisplatin. Inhibition of lung tumorigenesis has also been demonstrated in C3H mice treated with N-nitrosodiethylamine. In most of these experiments, reduction in tumor number and tumor size has been observed in the tea-treated group, and in some experiments, decreased tumor incidence has also been observed. The green tea constituent, epigallocatechin-3-gallate (EGCG), and the black tea constituent, theaflavins, have also been shown to be effective. Black tea preparations have been shown to reduce the incidence and number of spontaneously generated lung adenocarcinomas and rhabdomyosarcoma in A/J mice, as well as inhibit the progression of lung adenoma to adenocarcinoma. The mechanisms for the inhibitory action have not been well elucidated. It may be related to the antiproliferative, proapoptotic, and antiangiogenic activities of tea constituents that have been demonstrated in some experiments. These activities may be a result of the inhibition of key protein kinases involved in signal transduction and cell cycle regulation. Tea catechins, such as EGCG, have been suggested to be the effective components. However, a study suggests that caffeine is the key effective constituent for the inhibitory activity of lung tumorigenesis in Fisher 344 rats by black tea. In many of the experiments, tea consumption resulted in the reduction of body fat and body weight; these factors may also contribute to the inhibition of tumorigenesis.
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Affiliation(s)
- Chung S Yang
- Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, NJ 08854, USA.
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Lambert JD, Hong J, Yang GY, Liao J, Yang CS. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am J Clin Nutr 2005; 81:284S-291S. [PMID: 15640492 DOI: 10.1093/ajcn/81.1.284s] [Citation(s) in RCA: 288] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Many plant polyphenolic compounds have been shown to have cancer-preventing activities in laboratory studies. For example, tea and tea preparations have been shown to inhibit tumorigenesis in a variety of animal models of carcinogenesis, involving organ sites such as the skin, lungs, oral cavity, esophagus, stomach, liver, pancreas, small intestine, colon, and prostate. In some of these models, inhibitory activity was demonstrated when tea was administered during the initiation, promotion, or progression stage of carcinogenesis. The cancer-preventing activities of these and other polyphenols, such as curcumin, genistein, and quercetin, are reviewed. In studies in vitro, many of these compounds have been shown to affect signal transduction pathways, leading to inhibition of cell growth and transformation, enhanced apoptosis, reduced invasive behavior, and slowed angiogenesis. However, the concentrations used in cell culture studies were much higher than those found in vivo. If we propose mechanisms for cancer prevention on the basis of cell line experiments, then these activities must be demonstrated in vivo. The bioavailability, ie, tissue and cellular concentrations, of dietary polyphenols is a determining factor in their cancer-preventing activity in vivo. For example, compounds such as curcumin are effective when applied topically to the skin or administered orally to affect the colon but are not effective in internal organs such as the lungs. More in-depth studies on bioavailability should facilitate correlation of mechanisms determined in vitro with in vivo situations, increase our understanding of dose-response relationships, and facilitate extrapolation of results from animal studies to human situations.
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Affiliation(s)
- Joshua D Lambert
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA
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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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