Green Tea Extract Inhibition of Human Leiomyoma Cell Proliferation Is Mediated via Catechol-O-Methyltransferase (original) (raw)
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Green tea extract inhibits proliferation of uterine leiomyoma cells in vitro and in nude mice
American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL, 2010
Objective-Investigate the effect of epigallocatechin gallate (EGCG), on rat leiomyoma (ELT3) cells in vitro and in nude mice model. Study Design-ELT3 cells were treated with various concentrations of EGCG. Cell proliferation, PCNA and Cdk4 protein levels were evaluated. ELT3 cells were inoculated subcutaneously in female athymic nude mice. Animals were fed 1.25mg EGCG (in drinking water)/mouse/day. Tumors were collected and evaluated at 4 and 8 weeks post-treatment. Results-Inhibitory effect of EGCG (200 μM) on ELT3 cells was observed after 24 h treatment (p<0.05). At ≥50μM, EGCG significantly decreased PCNA and Cdk4 protein levels (p<0.05). In vivo, EGCG treatment dramatically reduced the volume and weight of tumors at 4 and 8 weeks posttreatment (p<0.05). The PCNA and Cdk4 protein levels were significantly reduced in EGCG treated group (p<0.05). Conclusion-EGCG effectively inhibits the proliferation and induce apoptosis in rat ELT3 uterine leiomyoma cells in vitro and in vivo.
Green tea is commonly used as a beverage worldwide, especially in China, Japan, Morocco, and Saudi Arabia. Green tea and its constituents have been considered very effective in the prevention and treatment of various diseases. It contains a variety of catechins, which show a pivotal role in the modulation of biological activities and also act as chemopreventive agents. Earlier studies have confirmed that green tea and its chief constituent epigallocatechin gallate (EGCG) have a potential role in the management of cancer through the modulation of cell signaling pathways. In this review, we focused on the beneficial effects of green tea and its constituents in the cancer prevention and treatment and its impact on modulation of molecular pathways.
Journal of cellular biochemistry, 2016
Uterine fibroids (leiomyomas) are very common benign tumors grown on the smooth muscle layer of the uterus, present in up to 75% of reproductive-age women and causing significant morbidity in a subset of this population. Although the etiology and biology of uterine fibroids are unclear, strong evidence supports that proliferation, angiogenesis and fibrosis are involved in their formation and growth. Currently the only cure for uterine fibroids is hysterectomy; the available alternative therapies have limitations. Thus, there is an urgent need for developing a novel strategy for treating this condition. The green tea polyphenol epigallocatechin gallate (EGCG) inhibits the growth of uterine leiomyoma cells in vitro and in vivo, and the use of a green tea extract (containing 45% EGCG) has demonstrated clinical activity without side effects in women with symptomatic uterine fibroids. However, EGCG has a number of shortcomings, including low stability, poor bioavailability and high metab...
Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells
Fertility and Sterility, 2010
To investigate the effects of epigallocatechin gallate (EGCG), an extract of green tea on cultured human leiomyoma cells (HuLM).Laboratory study.University hospitals.Not applicable.Not applicable.The HuLM cells were treated with various EGCG concentrations. Cell proliferation was assayed using Hoechst 33258 dye, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Total RNA was isolated, and gene expression profiling was performed on 84 key genes related to 18 different signal transduction pathways. The protein levels of PCNA, CDK4, BCL2, and BAX were examined by Western blot analysis.The HuLM cells treated with EGCG showed a dose-dependent and time-dependent inhibition of cell proliferation. The TUNEL staining indicated a significant increase in apoptosis in HuLM cells treated with 100 μM of EGCG compared with untreated control. Gene expression profiling indicated that EGCG treatment up-regulated representative genes from the transforming growth factor β (TGF-β) and stress pathways, while inhibiting the survival pathway and NFκB–dependent inflammatory pathway. Western blot analysis confirmed that EGCG at ≥50 μM significantly decreased the expression of PCNA, CDK4, and BCL2 as well as increased the expression of the proapoptotic BAX in a dose-dependent manner.Epigallocatechin gallate inhibits the proliferation of HuLM cells and induces apoptosis. These results suggest that EGCG may be a potential anti-uterine fibroid agent acting through multiple signal transduction pathways.
Cancer Letters, 1998
(−)-Epigallocatechin gallate (EGCG), a catechin polyphenol compound, represents the main ingredient of green tea extract. Although EGCG has been shown to be growth inhibitory in a number of tumor cell lines, it is not clear whether the effect is cancer-specific. In this study we compared the effect of EGCG on the growth of SV40 virally transformed WI38 human fibroblasts (WI38VA) with that of normal WI38 cells. The IC 50 value of EGCG was estimated to be 120 and 10 mM for WI38 and WI38VA cells, respectively. Thus, EGCG at 40 mM completely inhibited the growth of WI38VA cells, but had little or no inhibitory effect on the growth of WI38 cells. Similar differential growth inhibition was also observed between a human colorectal cancer cell line (Caco-2), a breast cancer cell line (Hs578T) and their respective normal counterparts. EGCG at a concentration range of 40-200 mM induced a significant amount of apoptosis in WI38VA cultures, but not in WI38 cultures, as determined by terminal deoxynucleotidyl transferase assay. After exposure to EGCG at 200 mM for 8 h, more than 50% of WI38VA cells in a confluent culture became apoptotic. In contrast, less than 1% of WI38 cells displayed apoptotic labeling under the same condition. EGCG did not affect the serum-induced expression of c-fos and c-myc genes in normal WI38 cells. However, it significantly enhanced their expression in transformed WI38VA cells. It is possible that differential modulation of certain genes, such as c-fos and c-myc, may cause differential effects of EGCG on the growth and death of cancer cells.
Frontiers in endocrinology, 2014
Physiological concentrations of the green tea extract epigallocatechin-3-gallate (EGCG) caused growth inhibition in estrogen receptor α (ERα)-positive MCF7 cells that was associated with down-regulation of the ERα and reduced insulin-like growth factor binding protein-2 abundance and increased protein abundance of the tumor suppressor genes p53/p21. In contrast to MCF7 cells that have wt p53, EGCG alone did not change cell proliferation or death significantly in another ERα-positive cell line T47D that possesses mutant p53. EGCG increased ERα protein levels and as a consequence, the cells responded significantly better to an ERα antagonist tamoxifen (TAM) in the presence of EGCG. EGCG significantly increased cell death in an ERα-negative cell line, MDA-MB-231 that also possesses mutant p53. EGCG significantly increased the ERα and insulin-like growth factor-I receptor levels and thereby enhanced the sensitivities of the cells to TAM and a blocking antibody targeting the insulin-like...
Genotoxic Effects of Green Tea Extract on Human Laryngeal Carcinoma Cells In Vitro
Archives of Industrial Hygiene and Toxicology, 2011
Genotoxic Effects of Green Tea Extract on Human Laryngeal Carcinoma Cells In VitroGreen tea (Camellia sinensis) contains several bioactive compounds which protect the cell and prevent tumour development. Phytochemicals in green tea extract (mostly flavonoids) scavenge free radicals, but also induce pro-oxidative reactions in the cell. In this study, we evaluated the potential cytotoxic and prooxidative effects of green tea extract and its two main flavonoid constituents epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on human laryngeal carcinoma cell line (HEp2) and its cross-resistant cell line CK2. The aim was to see if the extract and its two flavonoids could increase the sensitivity of the cisplatin-resistant cell line CK2 in comparison to the parental cell line. The results show that EGCG and green tea extract increased the DNA damage in the CK2 cell line during short exposure. The cytotoxicity of EGCG and ECG increased with the time of incubation. Green tea extra...
Carcinogenesis, 2000
nitrosodiethylamine-induced forestomach and lung tumors in 7322, USA mice and that both GTE and black tea extract (BTE) inhibited Email:vsly@nih.gov 4-(methylnitrosoamino)-1-butanone-induced lung adenomas, Black tea extracts (hot aqueous, polyphenols and theaflavalso in mice. Recently Rodgers et al. (21) showed black tea ins) and green tea extracts (hot aqueous, polyphenols, consumption could decrease mammary cancer in rats on high epicatechin, epicatechin gallate, epigallocatechin and epifat diets. gallocatechin gallate) were tested in nine standardized cell There has been extensive research into the possible mechanculture assays for comparative cancer chemopreventive isms of cancer prevention by tea extracts. Such mechanistic properties. Most black and green tea extracts strongly studies, especially with green tea polyphenols (GTPs) and inhibited neoplastic transformation in mouse mammary epigallocatechin gallate (EGCG), include inhibition of free organ cultures, rat tracheal epithelial cells and human lung radical formation and lipid peroxidation (22-31), the inhibition tumor epithelial cells. Nearly all tea fractions strongly of ornithine decarboxylase (ODC) (32-34), and the inhibition inhibited benzo[a]pyrene adduct formation with human of DNA-carcinogen binding and adduct formation (32,35).
Green Tea Catechins as Novel Antitumor and Antiangiogenic Compounds
Current Medicinal Chemistry-Anti-Cancer Agents, 2002
The concept of cancer prevention by use of naturally occuring substances that could be included in the diet is under investigation as a practical approach towards reducing cancer incidence, and therefore the mortality and morbidity associated with this disease. Tea, which is the most popularly consumed beverage aside from water, has been particularly associated with decreased risk of various proliferative diseases such as cancer and atherosclerosis in humans. Various studies have provided evidence that polyphenols are the strongest biologically active agents in green tea. Green tea polyphenols (GTPs) mainly consist of catechins (3-flavanols), of which (-)-epigallocatechin gallate is the most abundant and the most extensively studied. Recent observations have raised the possibility that green tea catechins, in addition to their antioxidative properties, also affect the molecular mechanisms involved in angiogenesis, extracellular matrix degradation, regulation of cell death and multidrug resistance. This article will review the effects and the biological activities of green tea catechins in relation to these mechanisms, each of which plays a crucial role in the development of cancer in humans. The extraction of polyphenols from green tea, as well as their bioavailability, are also discussed since these two important parameters affect blood and tissue levels of the GTPs and consequently their biological activities. In addition, general perspectives on the application of dietary GTPs as novel antiangiogenic and antitumor compounds are also presented.
Apoptotic effect of green tea polyphenol (EGCG) on cervical carcinoma cells
Diagn Cytopathol, 2010
The objective of this study was to probe the apoptotic effect of green tea polyphenol epigallocatechin-3-gallate (EGCG) on cervical carcinoma cells. This study was conducted in Departments of Pathology and Biochemistry, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India over a span of one and half years from January 2005 to August 2006. Caspase-3 assay was performed on monocytes isolated from cervical carcinoma patients and cultured with EGCG; cytosmears and sections from cervical carcinoma tissue cultured with EGCG were prepared for the morphological evidence of apoptosis. EGCG in a dose of 5 lg/ml and 10 lg/ml increased the caspase-3 levels in human cells. Cytosmears and sections from cervical carcinoma tissue cultured with EGCG showed better differentiation and increased number of apoptotic cells as compared to non EGCG controls. The number of such cells was increased more in 48 hours than in 24 hours. EGCG in a dose of 5 lg/ml and 10 lg/ml promoted apoptotic preparedness of human cells and induced apoptotic change in cervical carcinoma cells. Diagn.