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Abstract

The polyphenol compositions of green tea (GT) and black tea (BT) are very different due to post-harvest processing. GT contains higher concentrations of monomeric polyphenols, which affect numerous intracellular signaling pathways involved in prostate cancer (CaP) development. BT polymers, on the other hand, are poorly absorbed and are converted to phenolic acids by the colonic microflora. Therefore, after consumption of GT, higher concentrations of polyphenols are found in the circulation, whereas after BT consumption the phenolic acid levels in the circulation are higher. The majority of in vitro cell culture, in vivo animal, and clinical intervention studies examine the effects of extracts of GT or purified (-)-epigallocatechin-3-gallate (EGCG) on prostate carcinogenesis. These studies provide strong evidence supporting a chemopreventive effect of GT, but results from epidemiological studies of GT consumption are mixed. While the evidence for a chemopreventive effect of BT is much weaker than the body of evidence with regard to GT, there are several animal BT intervention studies demonstrating inhibition of CaP growth. This article will review in detail the available epidemiological and human clinical studies, as well as animal and basic mechanistic studies on GT and BT supporting a chemopreventive role in CaP.

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... Green tea (GT) is produced from the leaves of the plant Camellia sinensis. The anti-cancer activities of GT have been demonstrated in several cancers including prostate, mammary gland, colon, pancreas, liver, esophagus and liver cancer [6,7]. The major bioactive components of GT are GT polyphenols (GTPs), mainly including (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin (EC), and (-)-epicatechin-3-gallate (ECG), with EGCG as the most abundant and most bioactive component [6]. ...
... The tumor inhibitory effect through the inhibition of NFκB pathway was also demonstrated in previous studies [32]. In addition, our data demonstrated that a decrease in tissue protein content of a variety of growth factors including VEGF may play an important role in the reduction of tumor growth by GTP, Q and Doc [7,33]. ...
Article
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Background Chemotherapy with docetaxel (Doc) remains the standard treatment for metastatic and castration-resistance prostate cancer (CRPC). However, the clinical success of Doc is limited by its chemoresistance and side effects. This study investigated whether natural products green tea (GT) and quercetin (Q) enhance the therapeutic efficacy of Doc in CRPC in mouse models. Methods Male severe combined immunodeficiency (SCID) mice (n = 10 per group) were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. When tumors were established the intervention started. Mice were administered with GT + Q, Doc 5 mg/kg (LD), GT + Q + LD Doc, Doc 10 mg/kg (HD) or control. The concentration of GT polyphenols in brewed tea administered as drinking water was 0.07 % and Q was supplemented in diet at 0.4 %. Doc was intravenously injected weekly for 4 weeks, GT and Q given throughout the study. Results GT + Q or LD Doc slightly inhibited tumor growth compared to control. However, the combination of GT and Q with LD Doc significantly enhanced the potency of Doc 2-fold and reduced tumor growth by 62 % compared to LD Doc in 7-weeks intervention. A decrease of Ki67 and increase of cleaved caspase 7 were observed in tumors by the mixture, along with lowered blood concentrations of growth factors like VEGF and EGF. The mixture significantly elevated the levels of tumor suppressor mir15a and mir330 in tumor tissues. An increased risk of liver toxicity was only observed with HD Doc treatment. Conclusions These results provide a promising regimen to enhance the therapeutic effect of Doc in a less toxic manner.
... EGCG stands for (-)-epigallocatechin-3-gallate ( Figure 1) and is the most abundant flavan-3-ol in green tea. EGCG has been shown by various in vitro and animal studies to possess potential for preventing and treating prostate cancer [11]. The combination of 5-10 µM curcumin and 40 µM EGCG has been revealed by one study to improve synergistically the in vitro antiproliferative effects by 40% in androgen-sensitive LNCaP prostate cancer cells as compared with their individual treatments [12]. ...
... Green tea crude extracts have been designated as green tea catechins that consist of a group of naturally occurring flavan-3-ols, with (-)-epigallocatechin-3-gallate (EGCG) as the most abundant one. Green tea catechins and EGCG have been demonstrated by several in vitro cell-based assays and in vivo animal studies to have potential in preventing and treating prostate cancer [11]. Several studies as shown in the following subsections have suggested that either green tea catechins or EGCG might be even more effective as anti-prostate agents when they synergistically act with other natural or non-natural compounds. ...
Article
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This review is to describe synergistic effects of various combinations of dietary natural products including curcumin, quercetin, soybean isoflavones, silibinin, and EGCG that have potential for the treatment of prostate cancer. These data can provide valuable insights into the future rational design and development of synergistic and/or hybrid agents for potential treatment of prostate cancer.
... Still, in some types of neoplastic disease as prostate or lung cancer there was moderate evidence of risk reduction shown, while in others as gastric or urinary bladder cancer no effect was observed [1]. Recent exploratory meta-analysis of 13 observational studies confirmed borderline significant association between high green tea consumption and lower prostate cancer risk, with significant ameliorating effect observed in case-control studies (OR = 0.43) [59]. Still, it should be emphasized that regulatory authorities in Europe and USA are not as yet satisfied with abovementioned evidence. ...
... Epidemiological data concerning black tea effects are even more scant and generally suggest much weaker effect if any. In the citied meta-analysis no statistically significant association was observed between black tea consumption and cancer risk [59]. Numbers of studies provide data on the use of green tea or green tea polyphenols to enhance the effectiveness of chemo/radiotherapy. ...
Article
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Tea is one of the most popular beverages in many countries and is the second, after the pure water, most consumed drink in the world, but consumption habit varies between different countries. Incidence of different diseases varies widely across the world and many investigators relate these differences to diet including habitual tea drinking. It is consumed mostly as green tea and black tea where other forms such oolong; red or white teas are less popular. Green tea was extensively investigated on its health benefits but black tea is only now catching the serious attention of scientific community. Compounds contained in black tea such as theaflavins and thearubigens contribute to black tea dark color and distinctive flavor. They also provide health benefits originally attributed solely to green tea. This review summarizes available information on bioactive ingredients of tea, their bioactivity and relation to diseases, bioavailability with special attention to health benefits of black tea.
... EGCG is the most abundant constituent, consisting approximately 50% (wt/wt) of green tea catechins. The potential of green tea catechins (crude extracts) and pure EGCG in preventing and treating various cancers has been verified by extensive in vitro and in vivo studies from several research groups over the past 20 years [175]. ...
... The in vivo antitumor efficacy of green tea catechins and EGCG has been reviewed in detail in two review articles [175,184]. The first in vivo study of green tea catechins was initiated in 1995 by Liao and co-workers [185]. ...
Article
The term "flavonoids" is created for a big class of polyphenolic compounds featuring two aromatic rings (A and B) and a central heterocyclic ring C. More than 4,000 flavonoids have already been obtained throughout the plant kingdom. An inverse correlation between the intake of dietary flavonoids and the incidence of prostate cancer can be generally well-observed from several epidemiological studies worldwide, which encouraged several research groups to examine both in vitro and in vivo the potential of whole extracts of flavonoid-enriched dietary plants and purified flavonoids in preventing and treating prostate cancer. Nine subclasses of naturally occurring dietary flavonoids have so far been explored and identified to possess clinical potential in preventing and treating prostate cancer. We review herein the anti-prostate cancer potential (including in vitro potency, in vivo efficacy, and clinical studies), structure-activity relationships, and the mechanism of actions of the nine subclasses of naturally occurring flavonoids.
... has proved the radioprotective efficacy of tea as it reduced genotoxic injuries in rats. Other research carried out targeting the chemical constituents of this beverage for human health include [12][13][14][15][16][17][18][19][20][21]. The determination of Heavy metals and radionuclides in beverages, water, food, plant and soil, being the current subject of study, has been grabbing the attention of researchers significantly as these elements are not biodegradable, remain in the environment and pass to the food chain [9,[22][23][24][25]. ...
... However, the low bioavailability of most phytochemicals, like green tea polyphenols (GTPs, chemical structures in Figure 1A), and their extensive metabolism in vivo limit their anticancer efficacy in humans. Effective doses, as demonstrated in in vitro studies, are challenging to achieve in vivo through oral consumption and at safe levels [9,10]. Green tea (GT) is produced from the leaves of the plant Camellia sinensis, with epigallocatechin-3-gallate (EGCG) as the most abundant and bioactive component [11]. ...
Article
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The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of Arctium lappa, with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.
... Both In vivo and In vitro scientific studies report that EGCG results in the prevention of angiogenesis and tumor cell proliferation inhibition in numerous kinds of tumors (promoted by VEGF), such as prostate, colon, esophagus, and breast. [47,48] Polyphenols present in coffee have enhanced energy metabolism along with the reduction in abdominal and liver fat accumulation. [49] Caffeine is significant in suppressing fat absorption. ...
Article
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The aim of this review is develop to phytochemicals-based functional products against obesity and cancer management. Natural products have been made from reliable sources in past centuries. Phytochemicals are natural compounds that are available in vegetables, legumes, tea crops, fruits and various spices. Phytochemicals are known as secondary metabolites including carotenoids, phenolics, flavonoids, alkaloids, terpenes, saponins, cyanogenic glycosides, and glucosinolates. These phytochemicals are played direct or indirect role against several chronic diseases. However, these compounds have ability to act against various chronic diseases containing diabetes, hypertension, obesity, and cardiovascular diseases (CVDs). The literature reports the different potential properties of dietary phytochemicals such as anti-oxidants, anti-inflammatory, anti-viral, and anti-bacterial activities.
... Tea, especially green tea, has shown potential in preventing prostate cancer based on pre-clinical and preliminary clinical studies (reviewed by Henning et al. [148]). Our studies have also demonstrated that green tea and quercetin could significantly enhance the therapeutic effect of docetaxel in vitro and in mouse models at no increased risk of side effects [149,150]. ...
Article
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Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made prostate cancer treatment become more intensive and aggressive. Many phytochemicals isolated from plants have shown to be tumor cytotoxic. In vitro laboratory studies have revealed that natural compounds can affect cancer cell proliferation by modulating many crucial cellular signaling pathways frequently dysregulated in prostate cancer. A multitude of natural compounds have been found to induce cell cycle arrest, promote apoptosis, inhibit cancer cell growth, and suppress angiogenesis. In addition, combinatorial use of natural compounds with hormone and/or chemotherapeutic drugs seems to be a promising strategy to enhance the therapeutic effect in a less toxic manner, as suggested by pre-clinical studies. In this context, we systematically reviewed the currently available literature of naturally occurring compounds isolated from vegetables, fruits, teas, and herbs, with their relevant mechanisms of action in prostate cancer. As there is increasing data on how phytochemicals interfere with diverse molecular pathways in prostate cancer, this review discusses and emphasizes the implicated molecular pathways of cell proliferation, cell cycle control, apoptosis, and autophagy as important processes that control tumor angiogenesis, invasion, and metastasis. In conclusion, the elucidation of the natural compounds’ chemical structure-based anti-cancer mechanisms will facilitate drug development and the optimization of drug combinations. Phytochemicals, as anti-cancer agents in the treatment of prostate cancer, can have significant health benefits for humans.
... Recently, its incidence has rapidly increased due to the aging of the population, and interest in the use of natural products is increasing to overcome the various side effects of the drugs to treat BPH [20]. Therefore, we prepared BenPros by mixing plant-derived extracts of green tea extract, soybean extract, and camellia japonica oil, which are known to have anti-inflammatory and prostate protective effects [21][22][23], and evaluated its BPH protective effect. ...
Article
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Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men and causes lower urinary tract symptoms due to excessive proliferation of prostate stromal and epithelial cells. The present study investigated the improving effect of BenPros, an edible natural product mixture (green tea extract, soybean extract and camellia japonica oil), against the development of BPH in vitro and in vivo. BenPros treatment showed inhibitory ability on testosterone-induced androgen receptor, prostate-specific antigen (PSA), and 5α-reductase protein expression in LNCap-LN3 cells and anti-inflammatory effects on LPS-induced increases in interleukin-6 and tumor necrosis factor-α in RAW264.7 cells. In a testosterone propionate (TP)-induced BPH rat model, BenPros decreased the up-regulated serum 5α-dihydrotestosterone and PSA levels. Moreover, BenPros also significantly reduced PSA protein expression in prostate tissue. Furthermore, TP-induced increased expression of cyclooxygenase 2 and B-cell lymphoma 2 (Bcl-2) were reduced by BenPros, resulting in an increase in the Bcl-2/BCL2-related X ratio. These regulatory abilities of BenPros on BPH inducing markers also reduced prostate size and epithelial thickness based on histological analysis. These results indicate that BenPros has a protective ability against BPH in vitro and in vivo, and it may be a promising candidate as a functional food in regulating BPH.
... China has a long history of wine-drinking to dispel wind and cold, as well as to prevent aspects of diseases effectively. 1 Simultaneously, tea-drinking is also a Chinese traditional custom due to its various healthcare functions promoted by polyphenol, caffeine and the like in tea. [2][3][4][5] On the basis of tradition, Chinese people creatively began to make wine with tea leaves and invented a new alcoholic drink: Chinese tea wine. During the process of making tea wine, most of the nutritional and functional components of the tea are dissolved in the wine, such that the drink integrates the advantages of both tea and wine, and has extremely high pharmacological and healthcare functions. ...
Article
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Tea wine is a Chinese traditional alcoholic drink made by cereal and tea leaves. It is rich in tea polyphenols, caffeine, amino acids, and protons and possesses various healthcare functions. In this work, electrochemical methods, as well as density functional theory (DFT) calculations, were adopted to reveal the proton-coupled electron-transfer process of catechin in tea wine. The electrochemical results showed that the catechin preferred hydrogen-bonding with ethanol and formed molecular clusters. Thus, the direct electron-transfer process of catechin changed to proton-coupled electron transfer. This procedure reduced the energy barrier of the redox reaction and enhanced the anti-oxidative capacity. Subsequently, DFT calculations were employed to explore the bond length, bond energy, and HOMO-LUMO energy gap of catechin, which confirmed the above-mentioned mechanism. Our work offers some positive value for the scientific promotion of traditional food and a greater understanding of the health mechanisms in terms of chemistry.
... Another explanation is that the polyphenols exposure dose from daily tea drinking in human studies was much lower than the dose of the pure compounds in the experimental studies, though animal studies found a significantly protective effect (Chen and Lin, 2015). Besides, different tea types such as green tea and black tea might exert different effects on cancer prevention because of varying fermentation procedures or constituents within the tea (Gao et al., 2009;Henning et al., 2011;Yang et al., 2011), which might further mask the real association between tea consumption and risk of EC. ...
Article
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The association between tea drinking and esophageal cancer is still contradictory. This study is to determine the association between tea drinking and esophageal squamous cell carcinoma focusing on drinking temperature and tea types. A population-based case-control study was conducted in a high esophageal squamous cell carcinoma risk area in China. A total of 942 incident esophageal squamous cell carcinoma cases with historical confirmation and 942 age- and sex- individually matched community controls were recruited from the study area. Trained interviewers using a structured questionnaire collected detailed information on tea drinking, diet, smoking and alcohol drinking habits. Habitual tea drinking temperature was measured with a thermometer during interviews. We analyzed the association between tea consumption, drinking temperature and esophageal squamous cell carcinoma, stratified by tea type, while adjusting for other potentially confounding factors. Drinking very hot tea (>65°C) was significantly associated with the increased risk of esophageal squamous cell carcinoma (odds ratio = 1.67, 95% confidential interval 1.25-2.24) relative to non-drinkers. Consumption of black tea, irrespective of the frequency, intensity and tea leaf amount, was significantly associated with a higher risk (P for trend <0.01). Compared to those who consumed <300 g/month tea leaves at ≤65°C, those who consumed more than 300 g/month tea leave at >65°C had a more than 1.8-fold higher risk of esophageal squamous cell carcinoma for both green tea and black tea. Our results provide more evidence that drinking very hot tea (above 65°C) are significantly associated with an increased risk of esophageal squamous cell carcinoma.
... In relation to prostate cancer, it is found that tea polyphenols could prevent the growth of prostate cancer in animal model studies [19,38] , the results from a comparative study on the chemopreventive effect of black tea and green tea provided evidence that green tea has the stronger chemopreventive effect [39] . An exploratory meta-analysis of observational researches on green tea and black tea consumption and prostate cancer risk revealed that green tea drinking may have a protective effect on prostate cancer in Asian populations, especially in the Chinese population, while black tea drinking did not exhibit protective effects on prostate cancer [40] . ...
Article
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This article aims to provide currently available data and insight science knowledge on association between teas, their polyphenols and the risk of cancers including prostate, liver, lung, gastric, breast, colon and colorectal, esophageal, oral cavity, non-hodgkin’s lymphoma, esdometrial, and pancreatic based on published studies by searching Pub Med and database of Web of Science belonging Institute for Science Information and secondary referencing qualified for inclusion. In addition, the molecular mechanisms of tea in cancer prevention also briefly discussed. The authors hope that this work will be help for readers, researches, reviewers, and editors who are interested in the related field of the Camellia sinensis tea studies.
... It has been proved that TF in their gallate form exhibits stronger antioxidant activity as compared with individual TF moiety (Nagao et al., 2009). It has also been reported that in vivo free radical scavenging activity is moderately influenced by the value of standard one-electron potential (Table 3), higher in black tea polyphenols (BTP) as compared with vitamin C and tocopherol (Henning et al., 2011). TF also possess ability to inhibit prooxidative enzymes. ...
... EGCG affects many intracellular signaling pathways which are involved in development of prostate carcinoma. Thus it prevents the risk of prostate cancer (Henning et al. 2011;Zheng et al. 2011). ...
Chapter
Medicinal plants possess chemical constituents and produce secondary metabolites having countless benefits regarding various ailments. The extract of these plants can act as anti-inflammatory, antioxidative, anti-allergic, anti-cancerous, analgesic, and antidiabetic. Due to these medicinal properties, these plants have been used since centuries for the cure and prevention of different kind of diseases. Derivatives from the medicinal plants and their extracts are effective in small amounts, economical, and safe to use, with negligible side effects. Moreover, medicinal plants are easily accessible and have better compatibility. Review of the literature proves that countless medicinal plants have been exploited for their antitumor as well as anticancer potential. This chapter intends to focus on these plants showing medicinal effects against cancer and tumor. The chapter digs into the detail methodologies through which daily usage plants can be explored for medicinal purposes, the preparation of extracts, and the physiological responses of body towards these extracts.
... The low concentration and low bioavailability of active components in natural plants limited their clinical application [13]. It is reported that chemotherapeutic combination approaches could reach a greater effect than with one active compounds single at equal concentrations [10], which is called a synergistic effect. ...
Article
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Consumption of soybean products has been implicated in the prevention of breast cancer. This study provides insights into the anti-proliferative activity of 12 anticarcinogens from soybean by single or two-way combination treatment against MCF-7 and MDA-MB-231 human breast cancer cells. Results showed that genistein, daidzein, glycitein, genistin and dainzin showed stronger anti-proliferative activity against MCF-7 cells with EC50 values of 66.98 ± 4.87 μM, 130.14 ± 2.10 μM, 190.67 ± 5.65 μM, 72.82 ± 2.66 μM and 179.21 ± 6.37 μM, respectively. There is a synergistic effect of combination treatment of genistin plus daidzin in MCF-7 cells with combination index at inhibition of 50% (CI50) of 0.89 ± 0.12. Genistein, glycitein, genistin and β-sitosterol were demonstrated to have a stronger anti-proliferative activity against MDA-MB-231 cells with EC50 values of 93.75 ± 5.15 μM, 142.67 ± 5.88 μM, 127.82 ± 4.70 μM and 196.28 ± 4.45 μM. The synergistic effect was observed in the mixture of genistein plus genistin, genistein plus β-sitosterol or β-sitosterol plus genistin with CI50 values of 0.56 ± 0.13, 0.54 ± 0.20 and 0.45 ± 0.12, respectively. These bioactive anticarcinogens were able to inhibit invasion and migration of breast cancer cells and the combination treatments enhanced the inhibitory effect. Regulation of PI3K/Akt/mTORpathway seems to be the main mechanisms involved in the anticancer activity.
... A lot of scientific data attributed the pharmacological impacts of black tea to its phenolic contents [10]. TRs and TFs are the major polyphenols playing the key roles of potential antioxidants in the regulation of apoptosis, cell proliferation and aging in the cell lines of human cancer [4,11]. Also, TRs, theanine, and TFs are important quality elements of black tea which contribute to the color and taste in addition to their therapeutic impacts. ...
Article
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Medicinal plants are essential parts of traditional medicine due to their phytochemical constituents having pharmacological values and therapeutic properties. Black tea have thousands of various biological compounds such as flavanols (Thearubigins (TRs) and theaflavins (TFs) and catechins), amino acids (L.theanine), vitamins (A, C, K), flavonols (Quercetin, kaempferol, myricitin), lipids, proteins, volatile compounds carbohydrates, β-carotene and fluoride that illustrated many promising pharmacological effects regarded as growth promoter, cardioprotector, potent cholesterol-lowering effect, antioxidant and antimicrobial, etc inhuman. Although there is an exponential growth in molecular evidence of cholesterol-lowering and antioxidant effect in human, there is still a lack of information of the pharmacological effects of black tea. To fill this information gap, therefore, this review article underscores broadening the new insight pertaining to black tea that could be used as safe food additive. This article also illuminates the interesting role of black tea as an herbal medicine that is the future demand to get rid of synthetic health promoters in the human health practice. Moreover, this information would be useful in terms of the low-cost practice of natural medicines with no residual effects, and a natural protection of the human being. In addition, further studies at a molecular level are needed to reveal its mechanism of action particularly for the hypocholesterolemic effect of black tea to overcome the heart-related diseases, fewer side effects and being a natural safeguard of human health.
... Polyphenols may play a role for PCa prevention and treatment (van Die et al., 2016;Adhami et al., 2012;Davalli et al., 2012;Henning et al., 2011;Nguyen et al., 2012;Patel, 2014). Potential mechanisms by which they exert their anti-cancer activity include proliferation inhibition, apoptosis induction, and cell cycle arrest (Athar et al., 2007;Bhuvaneswari and Nagini, 2005;Cheung et al., 2010;Cipolla et al., 2015;Faria and Calhau, 2011;Juge et al., 2007;Li et al., 2014;Mahmoud et al., 2014;Pandey and Gupta, 2009;Ren et al., 2012;Shehzad et al., 2013). ...
Article
Polyphenols are secondary metabolites of plants. They comprise several antioxidant compounds and they are generally considered to be involved in the defense against human chronic diseases. During the last years, there has been growing scientific interest in their potential health benefits. In this comprehensive review, we focus on the current evidence defining the position of their dietary intake in the prevention/treatment of human chronic diseases, including prostate cancer and other types of cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases such as Alzheimer's and Parkinson's disease; we also discuss their ability to modulate multiple signalling transduction pathways involved in the pathophysiology of these diseases. Despite the fact that data regarding the biological functions of polyphenols can be considered exhaustive, evidence is still inadequate to support clear beneficial effects on human chronic diseases. Currently, most data suggest that a combination of phytochemicals rather than any single polyphenol is responsible for health benefit. More studies investigating the role of polyphenols in the prevention of chronic human diseases are needed, especially for evaluating factors such as gender, age, genotype, metabolism and bioavailability.
... The various tea types are classified on the basis of their manufacturing processes that influence taste, colour, and polyphenolic content composition. During green tea production, the endogenous oxidase enzymes in tealeaves are heating inactivated so that GTPs are preserved [10]. Flavonoids are the major active polyphenolic components of dried green tea extracts, in which flavan-3-ols account for more than 10% by weight [11]. ...
Article
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Green tea catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human prostate cancer (PCa) chemoprevention. In the last decades, many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs’ anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets, including cell surface receptors, lipid rafts, and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, and interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentrations that cannot be achieved in vivo. Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs’ bioavailability through still poorly understood mechanisms. Recent efforts to develop delivery systems that increase GTCs’ overall bioavailability, by means of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.
... GTP has been found to reduce oxidation in prostate cancer cells, preventing further mutations and metastasis. Henning et al. (2011) have shown that EGCG indirectly assist in stimulating the antioxidant response through upregulation of Nrf2 transcription factor. Nrf2 stimulation increases the expression of multiple antioxidant enzymes through the antioxidant-response element. ...
... Bu çalışmaların çoğunda saflaştırılmış epigallokateşin-3-gallat veya yeşil çaydan izole edilmiş polifenolik fraksiyonlar kullanılmıştır. 53 Prostat kanseri ile siyah çay (11 çalışma) ve yeşil çay tüketimi (7 çalışma) arasındaki ilişkiyi inceleyen çalışmaları içeren bir meta analizde, yeşil çayın (siyah çay değil) prostat kanserine karşı koruyucu özelliğinin olabileceği rapor edilmiştir. Yeşil çay ile ilgili çalışmaların çoğunluğunun Asya toplumunda yürütüldüğü bildirilmiştir. ...
... In recent years, plants derivatives have received much attention for their possible utility in the chemoprevention and treatment of tumors. [16][17][18][19][20][21][22] Among the medicinal plants used for the treatment or prevention of cancer, only 84 species were subjected to rigorous studies and only 35.71% of these species were subjected to pharmacological studies to test their activity. 20 The most frequently cited species are Aloe vera (Aloaceae), Euphorbia tirucalli (Euphorbiaceae), and Tabebuia impetiginosa. ...
Article
Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.
... In the last few years the identification and development of phenolic compounds or extracts from different plants has become a major area of health and medical related research [6]. Data from literature indicate that 124 different phytochemicals can be found in pomegranate fruit; amongst these phytochemicals, high molecular weight polyphenols (e. g. ellagitannins and the pomegranate-peculiar punicalagin) are likely to mediate the protective effects against a wide range of oxidative and inflammatory disorders, including cancer [10]. Recovery of tannin/ phenolic compounds is commonly performed through a solvent extraction procedure, but at present an ambiguous data on the method and conditions for extraction are available. ...
Article
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Pomegranate (Punicagranatum L. ) fruit is widely being consumed and its fruit’s peel having hydrolysable ellagitannin (ETs: polyphenolic compound) is an underutilized industrial waste from commercial point of view. In this present study an economical and efficient technique has been explored for the production of purified ellagitannin powder from pomegranate peel. Ellagitannin was isolated from fresh and fermented peel, purified with Amberlite XAD- 16 resin packed column and converted into ellagitannin powder by vacuum drying. About 38 gpurified ellagitannin powder was obtained from 1 kg fresh pomegranate peel. Total ellagitannin content(TEC) was 89. 78-91. 78 % as GAE possessing antioxidant activity (AOA) of 91. 16-96. 21 % as DPPH. Cost estimation of purified ellagitannin powder preparation process was Rs. 5510 from 1 kg fresh pomegranate peel. Worth of purified ellagitannin powder (38 g) estimated Rs. 25441 in international market. Studied method can be adopted for commercial production of purified ellagitannin powder.
... Total catechins were 140 mg/g in green tea and 42 mg/g in black tea. Green tea contained 30−42% of catechins and 5−10% of flavonols in comparison to 3−10% and 6−8% in black tea 19 . EGCG, the most abundant catechin, is thought to be responsible for most of the biological activities of green tea. ...
Article
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The antioxidant properties of 20 herbs and 28 herbal teas were analysed in comparison with those of Camellia sinensis based on total phenolic content (TPC), free radical scavenging (FRS) activity, ferric reducing power (FRP) and ferrous ion chelating (FIC) ability. The main objective was to find out if there are herbs and herbal teas with antioxidant properties comparable to or superior than those of C. sinensis. Results showed that TPC, FRS and FRP of C. sinensis leaves outperformed all herbs. FIC values were however weaker than those of banaba and cashew leaves. TPC, FRS and FRP of C. sinensis teas outperformed all herbal teas except those of banaba, lemon myrtle and stevia. Eleven herbal teas displayed stronger FIC values than C. sinensis teas with those of banaba, spearmint and peppermint being the most potent. Overall, C. sinensis leaves and teas remain the king of antioxidants based on phenolic content and primary antioxidant properties of FRS and FRP, but not on secondary antioxidant properties of FIC.
... Tea polyphenols are attracting increasing attention due to their reputed beneficial effects on human health; some epidemiological and animal studies have shown that tea polyphenols exert protective effects against inflammation (Zar et al., 2014), and have anti-obesity (Huang et al., 2014;Huang, Liu, Dushenkov, Ho, & Huang, 2009), anti-diabetic (Sabu, Smitha, & Kuttan, 2012), and antibacterial activities (Goulas, Exarchou, Kanetis, & Gerothanassis, 2014;Sharma, Gupta, Sarethy, Dang, & Gabrani, 2012). They have also been implicated as chemo-preventers against the development of various forms of tumors (Dai & Mumper, 2010;Sato, 1999;Zhao et al., 2014b), which is attributed to their antioxidative activities of scavenging free radicals, nitric oxide and/or chelating transition metals such as iron and copper (Forester & Lambert, 2011;Mandel, Weinreb, Reznichenko, Kalfon, & Amit, 2006;Sohn et al., 1994), and effect on numerous intracellular signaling pathways (Henning, Wang, & Heber, 2011). There is an increasing interest in the protective effects of GTP on BaP-induced mutagenesis in the lung of rpsL (Muto et al., 1999), Big Blue (Jiang, Glickman, & de Boer, 2001), as well as against carcinogenesis induced by BaP (Luo, Liu, & Wang, 1995). ...
... Green tea has higher concentrations of polyphenols, while black tea consumption has been shown to increase phenolic acids levels. Though clinical and pre-clinical studies provide evidence of green tea showing stronger chemopreventive effects as compared to black tea, concrete evidence from epidemiological studies is missing [150]. Additionally there still remain concerns about the bioavailability of EGCG and toxicity associated with its long-term use in clinical settings. ...
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Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment.
... In relation to prostate cancer, Gupta et al. (2001) and Adhami et al. (2004) reported that tea polyphenols could inhibit the development of prostate cancer in an animal experiment, whereas in USA, Henning et al. (2011) compared the chemopreventive effects of green tea and black tea on prostate cancer. These studies included in vitro cell culture and in vivo animal and clinical trials, lending strong support for the chemopreventive effects of green tea, but the results from epidemiological studies of green tea consumption are mixed. ...
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... The natural product EGCG is a major catechin in green tea that contributes to beneficial therapeutic effects, including antioxidant, anti-inflammatory, anticancer, and immunomodulatory effects (19,20). Studies conducted on cell-culture systems and animal models, as well as human epidemiological studies, show that EGCG in green tea could afford protection against a variety of cancer types (21). Many studies have shown that EGCG produces an anticancer effect by modulating the activity of mitogen-activated protein kinases (MAPKs), Insulin-like growth factor 1 (IGF1) receptor, Akt, NFκB and hypoxiainducible factor 1α (HIF1α) (22)(23)(24)(25). ...
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The cancer stem cell (CSC) model postulates the existence of a small proportion of cancer cells capable of sustaining tumor formation, self-renewal and differentiation. Signal Transducer and Activator of Transcription 3 (STAT3) signaling is known to be selectively activated in breast CSC populations. However, it is yet to be determined which molecular mechanisms regulate STAT3 signaling in CSCs and what chemopreventive agents are effective for suppressing CSC growth. The aim of this study was to examine the potential efficacy of curcumin and epigallocatechin gallate (EGCG) against CSC and to uncover the molecular mechanisms of their anticancer effects. To suppress the CSC phenotype, two breast cancer cell lines (MDA-MB-231 cells and MCF7 cells transfected with HER2) were treated with curcumin (10 μM) with or without EGCG (10 μM) for 48 h. We used tumor-sphere formation and wound-healing assays to determine CSC phenotype. To quantify CSC populations, Fluorescence-activated cell sorting profiling was monitored. STAT3 phosphorylation and interaction with Nuclear Factor-kB (NFkB) were analyzed by performing western blot and immunoprecipitation assays. Combined curcumin and EGCG treatment reduced the cancer stem-like Cluster of differentiation 44 (CD44)-positive cell population. Western blot and immunoprecipitation analyses revealed that curcumin and EGCG specifically inhibited STAT3 phosphorylation and STAT3-NFkB interaction was retained. This study suggests that curcumin and EGCG function as antitumor agents for suppressing breast CSCs. STAT3 and NFκB signaling pathways could serve as targets for reducing CSCs leading to novel targeted-therapy for treating breast cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
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Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.
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Recent data strongly indicate a relationship between prostate health and gut microbiota, in which composition and physiological function strictly depend on dietary patterns. The bidirectional interplay of foods containing polyphenols, such as ellagitannins, condensed tannins, lignans, isoflavones, and prenylated flavonoids with human gut microbiota, has been proven to contribute to their impact on prostate health. Considering the attributed role of dietary polyphenols in the prevention of prostate diseases, this paper aims to critically review the studies concerning the influence of polyphenols’ postbiotic metabolites on processes associated with the pathophysiology of prostate diseases. Clinical, in vivo, and in vitro studies on polyphenols have been juxtaposed with the current knowledge regarding their pharmacokinetics, microbial metabolism, and potential interactions with microbiota harboring different niches of the human organism. Directions of future research on dietary polyphenols regarding their interaction with microbiota and prostate health have been indicated.
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Green Tea Catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human Prostate Cancer (PCa) chemoprevention.In the last decades many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets including, cell surface receptors, lipid rafts and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentration that cannot be achieved in vivo.Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs bioavailability through still poor understood mechanisms. Recent efforts to develop delivery systems that increase GTCs overall bioavailability, by mean of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.
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Tea (Camellia sinensis) is the second most commonly consumed beverage in the world, and its consumption has been associated with several important health benefits due in part to its high concentration of polyphenolic compounds. Tea varieties, including white, green, oolong, pu-erh, and black tea, are all produced fromthe sameplant but differ in postharvest processing. The level of oxidative processing fromwhite to black tea (low to high) drives changes in polyphenol profiles from monomeric polyphenols (catechins) to oxidative products (theaflavins and thearubigins) that convert the subtle yellow color of green tea to the distinctive red/copper color of oolong and black tea. Polyphenol compounds from green teas have been well studied; however, oxidative products are more difficult to characterize and may require a combination of analytical techniques for identification and quantification. This technical summary introduces the major polyphenols in tea and discusses the main steps of tea processing and instrumentation used for polyphenol analysis.
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Chapter
Tea that is obtained from leaves of the plant Camellia sinensis is subsequent to water and is the most extensively consumed drink in the world. Black, green, and oolong tea are the forms which are produced by the different processing and manufacturing techniques making them chemically different from each other resulting for around 75 %, 23 %, and 2 % of the global production, respectively (Kavanagh et al. 2001). Black tea is a rich source of complex antioxidants called theaflavins and thearubigins, whereas steamed and dried green tea contains simple antioxidants called catechins. Green tea has been used for centuries to treat and prevent chronic diseases in traditional Chinese medicine, but it is only lately known as an efficient chemopreventive agent against various cancers (Sueoka et al. 2001).
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The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower doses (< 2μM) significantly inhibited the proliferation of LNCaP and LAPC-4 cells by 30-50% at 48h compared to control, and inhibited WPE1-NA22 cells by 75%, while did not affect normal prostate epithelial cells. Male severe combined immunodeficiency (SCID) mice were implanted subcutaneously with LAPC-4 cells for in vivo studies. In one experiment, the intervention started one week after tumor implantation. Mice received arctigenin at 50mg/kg (LD) or 100mg/kg (HD) b.w. daily or vehicle control by oral gavage. After 6 weeks, tumor growth was inhibited by 50% (LD) and 70% (HD) compared to control. A stronger tumor inhibitory effect was observed in a second experiment where arctigenin intervention started two weeks prior to tumor implantation. Arc was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 μM in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker Ki67, total and nuclear androgen receptor, and growth factors including VEGF, EGF, and FGF-β were significantly decreased by Arc, along with an increase in apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and miR-21-5p. This study provides the first in vivo evidence of the strong anticancer activity of arctigenin in prostate cancer. The effective dose of arctigenin in vitro is physiologically achievable in vivo, which provides a high promise in its translation to human application.
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Cancer is one of the major causes of mortality worldwide, and despite desperate attempts, many patients still suffer from poor prognosis. Hence, efforts for discovering and developing more potent and effective anticancer agents continue. A growing body of research and experiments indicates the potential of some medicinal plants as a possible source of anticancer agents. In recent years, the health benefits of consuming green tea (derived from the plant Camellia sinensis) have been extensively documented. The ailments which can be treated and/or prevented include different types of cancer, heart and liver diseases, and neuroprotective and antioxidant activities. Many of these beneficial effects are related to tea catechins, particularly (-)-epigallocatechin-3-gallate (EGCG) content. Green tea consumption is also linked to the prevention of many types of cancer including breast, prostate, lung, colon, and stomach cancers. Moreover, cancer rates in Asian countries such as Japan and China where green tea is consumed in large quantities are significantly low according to epidemiological studies. These associations are confirmed by experiments with animals as well as cultured cancer cells. The use of EGCG instead of crude green tea extracts permitted studies to elucidate the mode of anticancer of green tea. Clinical studies demonstrating the prevention of cancer by green tea or by EGCG were recently questioned. The use of the nontoxic green tea or EGCG as anticancer agent is highly recommended.
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Natural and synthetic xanthone derivatives are well known for their ability to act as antioxidants and/or enzyme inhibitors. This paper aims to present a successful synthetic methodology toward xanthenedione derivatives and the study of their aromatization to xanthones. Additionally their ability to reduce Fe(III), to scavenge DPPH radicals, and to inhibit AChE was evaluated. The results demonstrated that xanthenedione derivative 5e, bearing a catechol unit, showed higher reduction capacity than BHT and, similar to quercetin, strong DPPH scavenging activity (EC50 = 3.79 ± 0.06 µM) and it was also shown to be a potent AChEI (IC50 = 31.0 ± 0.09 µM) compared to galantamine (IC50 = 211.8 ± 9.5 µM).
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This paper presents an easy, fast, low cost, and sensitive approach for the electrochemical determination of quercetin based on its intercalation into DNA double helix. Electrochemical studies of the interaction between quercetin and DNA showed a decrease in peak currents with a reduction in redox reversibility of quercetin in the presence of the DNA. The electrochemical behavior of quercetin at a chitosan-entrapped carbon nanotube paste electrode coated with DNA was studied. A considerable increase was observed in the oxidation signal of quercetin at the DNA-coated electrode compared with a DNA-free electrode, indicating the preconcentration of quercetin due to its interaction with the surface-confined DNA layer. After optimizing the main experimental parameters influencing the biosensor response, its performance was evaluated from an analytical point of view. Two linear dependences of the anodic peak current of quercetin on its concentration were observed in the ranges of 0.40-7.50 and 7.50-30.0 μmol/L, with LOD and LOQ of 0.039 and 0.13 μmol/L, respectively. The proposed biosensor was successfully applied to the analysis of black and green tea extracts for their quercetin content.
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Tea (Camellia sinensis L.) is the most popular flavored, functional, and therapeutic non-alcoholic drink that consumes by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids which exhibit a range of promising pharmacological property. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK may be the basis for how dose black tea prevent and cure cancer. In vitro and preclinical studies support the anti-cancer activity of black tea, however its effect under human trails is uncertain, though more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea in order to reveal its anti-cancer effect.
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This study compared the anti-proliferative and apoptotic effects of organic and non-organic Sabah tea on cancer cell lines. Anti-proliferative assays showed that the tea extracts were capable of inhibiting the growth of MCF-7 and HeLa cells. The IC50 values for MCF-7 and HeLa were 20.9 ± 2.6 to 39.3 ± 0.8 and 38.5 ± 3.8 to 42.0 ± 2.3 μg/mL, respectively. Statistical differences were observed in MCF-7 cells treated with organic and non-organic tea extracts. However, no differences were found in HeLa cells. Morphological changes were observed in both treated cell lines when compared with the untreated cells. However, the formation of DNA laddering was only observed in the treated MCF-7 cells. Reduction of BCL-2 expression was found in the treated MCF-7 cells but BAX expression was unaltered. In conclusion, the effect of different farming systems on the proliferation of cancer cells could be cell-type-dependent but they showed no obvious differences in their effects on preventing cancer cell growth and inducing apoptosis.Practical ApplicationsTea is well known for its various health benefits due to its bioactivity. The findings from this study will add valuable preliminary information regarding the potential of organic and non-organic tea as natural chemopreventive and chemotherapeutic agents. These findings will provide scientific evidence on health advantages that might result from organic food consumption; thus, consumers will be able to make more informed choices.
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The study aimed at investigating how the antioxidant food components (polyphenols) interact with the bacteria that represent the human intestinal microbiota. Seven species of bacteria (isolated from the human intestine, and bought as pure bacterial cultures in lyophilised form), used in the experiments, were Enterococcus caccae, Escherichia coli, Lactobacillus sp., Bacteroides galacturonicus, Bifidobacterium catenulatum, Ruminococcus gauvreauii and Eubacterium cylindroides. Plant material with known health-promoting properties and a long tradition of use in folk medicine, such as fresh fruits of raspberry, elderberry, cranberry, lingonberry, Japanese quince and cornelian cherry, dried goji and Schisandra berries, red onion, bear’s garlic, nettle, green tea and soybeans, as well as food supplements (commercial pharmaceutical products: spirulina, noni juice and Citrosept) provided the source of polyphenols. In addition, solutions of pure polyphenolic compounds (representing various flavonoid classes and stilbenes) were used. The latter included (+)-catechin, phloridzin, quercetin, rutin, kaempferol, naringin, naringenin, hesperidin, hesperetin and resveratrol as polyphenols being the most frequently eaten with human diets. At the first stage of the study, the material was examined for antioxidant activity, total polyphenol content, and polyphenolic profile. At the second stage, the effect exerted on individual bacteria species by pure polyphenols, plant extracts and food supplements, used in different concentrations, was evaluated. It was found that the natural antioxidant components and the polyphenolic compounds present in plant material produce various effects on intestinal bacteria, from stimulating, through neutral, up to bacteriostatic and bactericidal, depending on the bacteria species. For extracts showing inhibitory potential, the minimum inhibitory concentration (MIC) was determined. In search of mechanisms behind the antioxidant and antimicrobial activity of polyphenols, the role of the structural elements of their molecules was discussed. The third stage of the research concerned the impact of intestinal bacteria on the antioxidant potential and the concentration of selected antioxidant components present in plant material. The changes that occurred due to the influence of particular bacteria species were assessed. It was demonstrated that bacteria representing the physiological intestinal microbiota of humans may biotransform polyphenols through various pathways, producing derivatives of higher or lower antioxidant potential (which has health implications). The increase in antioxidant activity, however, may often be caused not by the metabolic changes of polyphenols, but by their release from the bonds with proteins or other components present in the reaction medium. The results of the study provided a basis for formulating practical guidance for the consumers of polyphenol-rich foods (among them dietary supplements) and for the food industry.
Chapter
This chapter presents the important tea-growing areas, the manufacture of different types of tea (green, white, oolong, and black), and the chemical constituents of tea. Flavonoids and other polyphenols are the most important constituents of tea, the foremost being catechins (flavanols), which are the most abundant flavanoids in fresh tea leaves. The conversion of catechins to theaflavins and thearubigins during the manufacture of oolong and black teas, and the chemistry of other flavonoids, such as flavonol and flavone glycosides, proanthocyanidins, and bisflavanols, are presented. Data on the content of these compounds are given and concepts for the differentiation of different types of tea (e.g., green and black tea) and the detection of geographic origin are discussed. The chemistry of non-flavonoids in tea, such as alkaloids, carotenoids, minerals, amino acids (especially l-theanine), carbohydrates, lipids, and volatiles/aroma compounds, is discussed. The brewing of tea and tea products (decaffeinated and instant teas, tea-based ready-to-drink beverages) is explained. The potential health benefits (e.g., anticancer effects, protection against cardiovascular heart disease) of tea and its constituents, foremost tea flavonoids, are described. This chapter includes a section on the bioavailability and metabolism of tea constituents. State-of-the-art analytical methods for the determination of selected tea constituents are listed.
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Although gallotannin contained in several medicinal plants was known to have multi-biological activities, such as antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and antitumor effects, the underlying apoptotic mechanism of gallotannin is not fully understood so far. Thus, in the present study, the apoptotic mechanism of gallotannin was elucidated in DU145, PC-3, and M2182 prostate cancer cells in association with myeloid cell leukemia 1 (Mcl-1) signaling. Gallotannin exerted dose-dependent cytotoxicity in DU145, PC-3, and M2182 prostate cancer cells. Also, gallotannin showed apoptotic morphological features and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and sub-G1 accumulation in three prostate cancer cell lines. Consistently, gallotannin cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of procaspases 9 and 3 in three prostate cancer cell lines. Furthermore, gallotannin attenuated the expression of survival genes such as Mcl-1, B-cell lymphoma 2, and B-cell lymphoma 2 extra large in three prostate cancer cell lines. Interestingly, overexpression of Mcl-1 reversed the ability of gallotannin to cleave PARP and increase sub-G1 population in three prostate cancer cell lines. Conversely, silencing of Mcl-1 enhanced apoptosis by gallotannin in three prostate cancer cell lines by FACSCalibur (Becton Dickinson, Franklin Lakes, NJ, USA). Taken together, our findings demonstrate that inhibition of Mcl-1 and activation of caspases are critically involved in gallotannin-induced apoptosis in prostate cancer cells. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Article
Five terpenoids (1–5) from a vegetable plant Acanthopanax trifoliatus (L.) Merr. were investigated for their effects on human prostate cancer cells. The diterpenoid (3) and triterpenoids (4 and 5) were found to inhibit the growth and stimulate apoptosis in PC-3 cells. The effects of these terpenoids on PC-3 cells were associated with strong suppression of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). These terpenoids also inhibited the expression of survivin, a downstream target of NF-κB and STAT3. The in vivo study using a xenograft mouse model showed that 5 strongly inhibited the formation and growth of PC-3 tumours. Moreover, treatment with 5 strongly decreased the expression of phospho-STAT3 and survivin in PC-3 tumours. Our results indicate that 5 has preventive efficacy on the development of PC-3 xenograft tumours. This terpenoid may serve as a candidate for future development as a novel agent for prostate cancer prevention.
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Flavanols of Camellia sinensis exhibit uric acid (UA) lowering effect, through the modulation of both xanthine oxidase and urate excretion. In order to investigate the potential benefit of Camellia Sinenis products in asymptomatic hyperuricaemia, a meta-analysis of long-term Randomized Controlled Trials (RCT) with tea or tea extract has been conducted. From 20 human intervention studies selected only 5 RCT (13 interventions) were suitable for meta-analysis (n=472). The current “normal” range set for hyperuricaemia fails to identify patients with potential metabolic disorders. Therefore on the basis of the literature data, we fixed cut off limits for UA baseline levels of 4.5 mg/dl for women, 6.1 mg/dl for men and 5.5 mg/dl for studies involving mixed populations. Statistically significant effects were not found, but subgroup analysis revealed that the Pooled Estimate effect was different in subjects with baseline levels under [MD (95% CI): 0.1078 (−0.0528 to 0.2684)] and over the cut off [MD (95% CI): −0.0239 (0.3311 to 0.2833)]. However, due to the low number of RCT and to the lack of data on bioavailability, it is difficult to draw any firm conclusion and more studies are needed to establish if tea flavanols could be useful in asymptomatic hyperuricaemia treatment.
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Chemotherapy with docetaxel (Doc) is a standard treatment for metastatic and castration-resistant prostate cancer. However, chemoresistance and side effects of Doc limit its clinical success. We investigated whether natural products green tea (GT) and quercetin (Q), a flavonoid from apples and onions, will enhance the efficacy of Doc in androgen-independent (AI) prostate cancer cells. Two cell lines including LAPC-4-AI and PC-3 were treated in vitro with 40μM of (-)-epigallocatechin gallate (EGCG), 5μM of Q, 2nM or 5nM of Doc alone or in combination. The mixture of EGCG+Q+Doc increased the anti-proliferative effect by 3-fold in LAPC-4-AI cells and 8-fold in PC-3 cells compared to Doc alone. EGCG, Q and Doc in combination significantly enhanced cell cycle arrest at G2/M phase and increased apoptosis in both LAPC-4-AI and PC-3 cells compared to Doc alone. The mixture increased the inhibition of PI3K/Akt and the signal transducer and activator of transcription (Stat) 3 signaling pathways compared to Doc alone, and decreased the protein expression of multidrug resistance-related protein (MRP1). In addition, the combination with EGCG and Q increased the inhibition of tumor cell invasion and colony formation in both LAPC-4-AI and PC-3 cells compared to Doc alone, and decreased the percentage of CD44+/CD24- stem-like LAPC-4-AI cells. In summary, GT and Q enhanced the therapeutic effect of Doc in castration-resistant prostate cancer cells through multiple mechanisms including the downregulation of chemoresistance-related proteins. This study provides a novel therapeutic modality to enhance the efficacy of Doc in a non-toxic manner.
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To elucidate the sequence of molecular events intricate with angiogenesis and the initiation and progression prostate cancer, the temporal and spatial expression patterns of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), hypoxia-induced factor-1 (HIF-1), vascular endothelial growth factor (VEGF), and the cognate receptors VEGFR1 and VEGFR2 were characterized. Immunohistochemical and in situ analyses of prostate tissue specimens derived from the spontaneous autochthonous transgenic adeno-carcinoma of the mouse prostate (TRAMP) model identified a distinct early angiogenic switch consistent with the expression of PECAM-1, HIF-1, and VEGFR1 and the recruitment of new vasculature to lesions representative of high-grade prostatic epithelial neoplasia (PIN). During progression of pros-tate cancer, the intraductal microvessel density (IMVD) was also observed to increase as a function of tumor grade. Immunoblot and in situ analyses further demonstrated a distinct late angiogenic switch consistent with de-creased expression of VEGFR1, increased expression of VEGFR2, and the transition from a differentiated adenocarcinoma to a more poorly differen-tiated state. Analysis of clinical prostate cancer specimens validated the predictions of the TRAMP model. This resolution of prostate cancer-associ-ated angiogenesis into distinct early and late molecular events establishes the basis for a "progression-switch" model to explain how the targets of antian-giogenic therapy might change as a function of tumor progression.
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Purpose This study examines the role of cell survival/apoptosis related proteins involved in NFκB signaling pathways and its associated events in GTP-induced chemoprevention of prostate cancer in TRAMP mice. Methods Mice were given 0.1% GTP as drinking fluid. Western blot and immunohistochemical analysis performed to examine NFκB and its regulated pathway in response to GTP. Results Our data demonstrated increased expression of NFκB, IKKα, IKKβ, RANK, NIK and STAT-3 in dorso-lateral prostate of TRAMP mice as a function of age and tumor growth and continuous GTP infusion for 32 weeks resulted in substantial reduction in these proteins. The levels of transcription factor osteopontin, a non-collagenous extracellular matrix protein, were also downregulated. Inhibition of NFκB signaling is known to activate apoptotic and inhibit anti-apoptotic proteins. Therefore, we analyzed Bax and Bcl2 levels in the dorsolateral prostate of TRAMP mice fed GTP and observed a shift in balance between Bax and Bcl2 favoring apoptosis. Conclusions Based on the data we suggest that oral consumption of GTP might inhibit osteopontin and NFκB signaling that may contribute to induction of apoptosis observed in GTP fed TRAMP mice.
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Green tea polyphenols (GTP) have been reported to inhibit DNA methylation in cultured cells. Here, we tested whether oral consumption of GTPs affects normal or cancer-specific DNA methylation in vivo, using mice. Wild-type (WT) and transgenic adenocarcinoma of mouse prostate (TRAMP) mice were given 0.3% GTPs in drinking water beginning at 4 weeks of age. To monitor DNA methylation, we measured 5-methyl-deoxycytidine (5mdC) levels, methylation of the B1 repetitive element, and methylation of the Mage-a8 gene. Each of these parameters were unchanged in prostate, gut, and liver from WT mice at both 12 and 24 weeks of age, with the single exception of a decrease of 5mdC in the liver at 12 weeks. In GTP-treated TRAMP mice, 5mdC levels and the methylation status of four loci hypermethylated during tumor progression were unaltered in TRAMP prostates at 12 or 24 weeks. Quite surprisingly, GTP treatment did not inhibit tumor progression in TRAMP mice, although known pharmacodynamic markers of GTPs were altered in both WT and TRAMP prostates. We also administered 0.1%, 0.3%, or 0.6% GTPs to TRAMP mice for 12 weeks and measured 5mdC levels and methylation of B1 and Mage-a8 in prostate, gut, and liver tissues. No dose-dependent alterations in DNA methylation status were observed. Genome-wide DNA methylation profiling using the HpaII tiny fragment enrichment by ligation-mediated PCR assay also revealed no significant hypomethylating effect of GTP. These data indicate that oral administration of GTPs does not affect normal or cancer-specific DNA methylation in the murine prostate.
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The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.
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The purpose of this study was to determine the effects of short-term supplementation with the active compounds in green tea on serum biomarkers in patients with prostate cancer. Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E, which contained 800 mg of (−)-epigallocatechin-3-gallate (EGCG) and lesser amounts of (−)-epicatechin, (−)-epigallocatechin, and (−)-epicatechin-3-gallate (a total of 1.3 g of tea polyphenols), until time of radical prostatectomy. Serum was collected before initiation of the drug study and on the day of prostatectomy. Serum biomarkers hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, IGF binding protein-3 (IGFBP-3), and prostate-specific antigen (PSA) were analyzed by ELISA. Toxicity was monitored primarily through liver function enzymes. Changes in serum components were analyzed statistically using the Wilcoxon signed rank test. Cancer-associated fibroblasts were treated with EGCG, and HGF and VEGF protein and mRNA levels were measured. HGF, VEGF, PSA, IGF-I, IGFBP-3, and the IGF-I/IGFBP-3 ratio decreased significantly during the study. All of the liver function tests also decreased, five of them significantly: total protein, albumin, aspartate aminotransferase, alkaline phosphatase, and amylase. The decrease in HGF and VEGF was confirmed in prostate cancer–associated fibroblasts in vitro. Our results show a significant reduction in serum levels of PSA, HGF, and VEGF in men with prostate cancer after brief treatment with EGCG (Polyphenon E), with no elevation of liver enzymes. These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer.
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As one of the most prevalent cancers, prostate cancer has enormous public health importance and its prevention seems to be a rational approach to attenuate the economic, emotional, physical, and social impact of this disease. This review discusses some of the options available to clinicians worldwide under the broad headings of chemoprevention and dietary modification including lifestyle issues. From the review of available literature, it is appreciated that although many exciting options such as androgen inhibitors, vitamin E, and selenium are being actively considered, they are far from being included in clinical practice. So until large randomized trials confirm the benefit of chemopreventives and dietary modifications, patients may be advised to pursue a diet and lifestyle that ensures overall fitness.
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We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP. GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF)-I/IGF binding protein-3 and IGF signaling. Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common. Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.
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A number of epidemiological studies suggest that the consumption of green tea reduces the incidence of prostate cancer. As the major catechins present in green tea are potent antioxidants, we hypothesized that genetic and cellular damage induced by oxygen free radicals could be significantly reduced by potent antioxidants in green tea, thus reducing the cumulative genetic and cellular damage with age, and slowing or preventing tumour formation. Long-term administration of a decaffeinated green tea extract to Lobund-Wistar rats for periods up to 26 months almost halved the incidence of primary tumours in the genitourinary tract when compared with an age-matched cohort receiving just water. We observed no inhibition of DNA adduct formation or lipid peroxidation in animals consuming green tea compared with animals consuming deionized water. The decrease in tumour formation was associated with an increase in 8-hydroxy-2'deoxyguanosine and 4-hydroxynonenal content (markers of DNA adduct formation and lipid peroxidation, respectively) in the epithelium of the ventral prostate in aging animals. In addition, there was an increase in 8-hydroxy-2'deoxyguanosine expression, but no change in 4-hydroxynonenal expression in the seminal vesicles of older animals. An age-associated increase in expression of the antioxidant enzymes manganese superoxide dismutase and catalase in the epithelium of the ventral prostate of aging animals was observed. Furthermore, there was also an increase in manganese superoxide dismutase expression, but no change in catalase expression in the seminal vesicles of older animals. These data demonstrate that consumption of green tea decreases the incidence of genitourinary tract tumours in the Lobund-Wistar rat, but has no effect on age-associated DNA adduct formation and lipid peroxidation in the ventral prostate and seminal vesicles of the aging rat.
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Following the report from Hawaii (Heilbrun et al., 1986) of relationships between tea consumption and respectively rectal cancer (positive) and prostate cancer (negative), these questions were examined using data from a prospective mortality study of London men initiated in 1967. The small numbers of men who did not usually drink any tea prevented a reliable study of this sub group. Nevertheless no evidence of a dose-response relationship was found for rectal, colon or prostate cancer. Significant relationships were found, however, between tea consumption and deaths from stomach, lung and kidney cancers. In the case of stomach and lung cancer, these were partly due to the effects of social class and smoking, and possible reasons are considered for the residual relations.
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In a prospective cohort study, men of Japanese ancestry were clinically examined from 1965 to 1968. For 7,833 of these men, data on black tea consumption habits were recorded. Since 1965, newly diagnosed cancer incidence cases have been identified: 152 colon, 151 lung, 149 prostate, 136 stomach, 76 rectum, 57 bladder, 30 pancreas, 25 liver, 12 kidney and 163 at other (miscellaneous) sites. Compared to almost-never drinkers, men habitually drinking black tea more than once/day had an increased relative risk (RR) for rectal cancer (RR = 4.2). This positive association (P = 0.0007) could not be accounted for by age or alcohol intake. We also observed a weaker but significant negative association of black tea intake and prostate cancer incidence (P = 0.020). There were no significant associations between black tea consumption and cancer at any other site.
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Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (Camellia sinensis), has shown cancer preventive activity in animal models. The bioavailability of EGCG in the most commonly used animal species, mice, is poorly understood. Moreover, the pharmacokinetic parameters of EGCG have not been reported previously in mice. Here we report that after administration of EGCG intravenously at 21.8 mumol/kg or intragastrically at 163.8 mumol/kg, the peak plasma levels of EGCG in male CF-1 mice were 2.7 +/- 0.7 and 0.28 +/- 0.08 mumol/L, respectively. EGCG was present mainly (50-90%) as the glucuronide. The plasma bioavailability of EGCG after intragastric administration was higher than previously reported in rats (26.5 +/- 7.5% vs. 1.6 +/- 0.6%). The conjugated EGCG displayed a shorter t(1/2) (82.8-211.5 vs 804.9-1102.3 min) than unconjugated EGCG (P < 0.01, Student's t test). EGCG was present in the unconjugated form in the lung, prostate and other tissues at levels of 0.31-3.56 nmol/g after intravenous administration. Although intragastric administration resulted in lower levels in most tissues compared with intravenous administration (e.g., 0.006 +/- 0.004 vs. 2.66 +/- 1.0 nmol/g in the lung), the levels in the small intestine and colon were high at 45.2 +/- 13.5 and 7.86 +/- 2.4 nmol/g, respectively. This is the first report of the pharmacokinetic parameters of EGCG in mice. Such information provides a basis for understanding the bioavailability of EGCG in mice and should aid in understanding the cancer preventive activity of EGCG. J. Nutr. 133: 4172-4177, 2003.
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Tumor growth and metastasis depend on the formation of blood vessels, angiogenesis, to supply the developing mass with nutrients, oxygen, and waste removal. The proteasome, a massive multisubunit catabolic body, exerts a regulatory influence on angiogenesis. Inhibition of the proteasome activity has been found to inhibit angiogenesis and induce apoptosis in human cancer cells with limited toxicity to normal cells. Therefore, the dual action of angiogenesis inhibition and cell death induction makes proteasome inhibition an attractive modality for chemotherapy. A variety of proteasome inhibitors have been studied including: antibiotics such as lactacystin, the green tea polyphenols, and the boronic acid Velcade (MLN-341). Most recently, certain classes of copper compounds have been found to act as potent proteasome inhibitors. The potential of particular organic compounds, such as 8-hydroxyquinoline, to spontaneously bind with tumor cellular copper and form proteasome inhibitors provides a new modality of anti-proteasome and anti-angiogenesis chemotherapy. This review examines angiogenesis, the proteasome, representative proteasome inhibitors, and the emerging role of copper. The formation of new blood vessels, or angiogenesis, is an important and necessary function in both embryonic development and wound repair [1, 2]. Therefore, the ability to regenerate or form new vessels for blood flow is essential. The control of angiogenic pathways is tightly regulated in normal differentiated adult cells, which generally do not stimulate blood vessel growth unless injury occurs. However, cancerous tissues stimulate angiogenesis that in turn leads to increased tumor formation and possible metastases [3]. Many of the factors involved in angiogenesis are regulated by the proteasome, which recently has become a focus in anti-cancer therapies due to its involvement in cell cycle and apoptosis control [4, 5]. Here we discuss angiogenesis and its relation to the proteasome. Additionally, current modalities of anti-angiogenic treatment, mainly proteasome inhibitory strategies, are reviewed. Furthermore, proteasome inhibitors, both natural and synthetic, and their anti-angiogenic effects as well as future approaches to anti-angiogenic chemotherapies are also discussed.
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Green tea (Camellia sinensis) is rich in catechins, of which (−)-epigallocatechin-3-gallate (EGCG) is the most abundant. Studies in animal models of carcinogenesis have shown that green tea and EGCG can inhibit tumorigenesis during the initiation, promotion and progression stages. Many potential mechanisms have been proposed including both antioxidant and pro-oxidant effects, but questions remain regarding the relevance of these mechanisms to cancer prevention. In the present review, we will discuss the redox chemistry of the tea catechins and the current literature on the antioxidant and pro-oxidative effects of the green tea polyphenols as they relate to cancer prevention. We report that although the catechins are chemical antioxidants which can quench free radical species and chelate transition metals, there is evidence that some of the effects of these compounds may be related to induction of oxidative stress. Such pro-oxidant effects appear to be responsible for the induction of apoptosis in tumor cells. These pro-oxidant effects may also induce endogenous antioxidant systems in normal tissues that offer protection against carcinogenic insult. This review is meant point out understudied areas and stimulate research on the topic with the hope that insights into the mechanisms of cancer preventive activity of tea polyphenols will result.
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Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer-related deaths in American males with similar trends in many western countries. The existing treatment approaches and surgical intervention have not been able to effectively cope with this dreaded disease. For these reasons, it is necessary to intensify our efforts for a better understanding of the disease process and for the development of novel approaches for its prevention and treatment. Based on considerable evidence from in vivo and in vitro data and epidemiological studies, in recent years the beverage tea has gained considerable attention for reducing the risk of several cancers. Much of the cancer preventive effects of tea, especially green tea appear to be mediated by the polyphenols present therein. Geographical evidence suggests that the incidence and occurrence of PCa is lower in populations that consume tea regularly. This evidence suggests that tea polyphenols could be extrapolated to optimize their chemopreventive properties against PCa. PCa represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age and therefore, even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. In this review we address the issue of possible use of tea, especially green tea, for the prevention as well as treatment of PCa.
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Objectives: To evaluate the relationship between prostate cancer and several potential lifestyle risk factors. Methods: We analyzed data obtained from a population-based case–control study conducted in eight Canadian provinces. Risk estimates were generated by applying multivariate logistic regression methods to 1623 histologically confirmed prostate cancer cases and 1623 male controls aged 50–74. Results: Cases were more likely to have a first-degree relative with a history of cancer, particularly prostate cancer (OR = 3.1, 95% CI = 1.8–5.4). Reduced risks of prostate cancer were observed among those of Indian descent (OR = 0.2, 95% CI = 0.1–0.5) or any Asian descent (OR = 0.3, 95% CI = 0.2–0.6) relative to those of western European descent. Total fat consumption, tomato and energy intake, were not associated with prostate cancer. The risk of prostate cancer was inversely related to the number of cigarettes smoked daily (p = 0.06) and cigarette pack-years (p < 0.01), while no association was observed between the total number of smoking years or the number of years since smoking cessation. Anthropometric measures and moderate and strenuous levels of leisure time physical activity were not strongly related to prostate cancer. In contrast, strenuous occupational activities at younger ages appeared protective. Conclusions: Our analyses are limited by the absence of data related to tumor severity and screening history. Further studies are needed to investigate the relationship between behavioral risk factors and prostate cancer screening practices.
Article
Prostate cancer (PCA) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the United States. Descriptive epidemiological data suggest that androgens and environmental exposures play a key role in prostatic carcinogenesis. Since androgen action is intimately associated with proliferation and differentiation, at the time of clinical diagnosis in humans most PCA represent themselves as a mixture of androgen-sensitive and androgen-insensitive cells. Androgen-sensitive cells undergo rapid apoptosis upon androgen withdrawal. On the other hand, the androgen-insensitive cells do not undergo apoptosis upon androgen blocking, but maintain the molecular machinery of apoptosis. Thus, agents capable of inhibiting growth and/or inducing apoptosis in both androgen-sensitive and androgen-insensitive cells will be useful for the management of PCA. In the present study, we show that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent present in green tea, imparts antiproliferative effects against both androgen-sensitive and androgen-insensitive human PCA cells, and this effect is mediated by deregulation in cell cycle and induction of apoptosis. EGCG treatment was found to result in a dose-dependent inhibition of cell growth in both androgen-insensitive DU145 and androgen-sensitive LNCaP cells. In both the cell types, EGCG treatment also resulted in a dose-dependent G0/G1-phase arrest of the cell cycle as observed by DNA cell-cycle analysis. As evident by DNA ladder assay, confocal microscopy, and flow cytometry, the treatment of both DU145 and LNCaP cells with EGCG resulted in a dose-dependent apoptosis. Western blot analysis revealed that EGCG treatment resulted in (i) a dose-dependent increase of p53 in LNCaP cells (carrying wild-type p53), but not in DU145 cells (carrying mutant p53), and (ii) induction of cyclin kinase inhibitor WAF1/p21 in both cell types. These results suggest that EGCG negatively modulates PCA cell growth, by affecting mitogenesis as well as inducing apoptosis, in cell-type-specific manner which may be mediated by WAF1/p21-caused G0/G1-phase cell-cycle arrest, irrespective of the androgen association or p53 status of the cells.
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The chemopreventive and chemoprotective activities of green tea have been attributed to the polyphenolic ingredient (−)-epigallocatechin-3-gallate (EGCG). Here, we report that treatment of human breast epithelial (MCF10A) cells with EGCG induces the expression of glutamate–cysteine ligase, manganese superoxide dismutase (MnSOD), and heme oxygenase-1 (HO-1). NF-E2-related factor (Nrf2) has been reported to regulate the antioxidant response element (ARE)-mediated expression of many antioxidant as well as detoxifying enzymes. The nuclear accumulation, ARE binding and transcriptional activity of Nrf2 were increased by EGCG treatment. Silencing of Nrf2 by siRNA gene knockdown rendered the MCF10A cells less sensitive to the EGCG-induced expression of HO-1 and MnSOD. Furthermore, EGCG activated Akt and extracellular signal-regulated protein kinase1/2 (ERK1/2). The pharmacologic inhibition of these kinases abrogated the nuclear translocation of Nrf2 induced by EGCG. These findings suggest that Nrf2 mediates EGCG-induced expression of some representative antioxidant enzymes, possibly via Akt and ERK1/2 signaling, which may provide the cells with acquired antioxidant defense capacity to survive the oxidative stress.
Article
Green tea and black tea (BT) contain gallated [(-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate] and nongallated [(-)-epicatechin, (-)-epigallocatechin (EGC)] tea polyphenols (PP). During BT production, PP undergo oxidation and form larger polymers such as theaflavins (THE) and thearubigins, which contribute to the health benefit of BT. This article gives an overview of the role of chemical characteristics and endogenous metabolism of tea PP and their bioavailability in humans and describes attempts to increase their bioavailability. At pH close to neutral, EGCG and EGC form homo- and heterodimers generating hydrogen peroxide. To confirm the pH instability of EGCG, EGC, and THE in cell culture medium, their antiproliferative activity was determined in the presence and absence of catalase. The antiproliferative activity in LNCaP prostate cancer cells was decreased when incubated with catalase prior to EGCG, EGC, and THE treatment. In addition, new findings demonstrated that the formation of methyl-EGC increased the stability at neutral pH compared with EGC. Approaches to increase the bioavailability of flavan-3-ols are reviewed, which include the administration of tea in combination with fruit juices, coadministration with piperine, and peracetylation of EGCG. Future intervention studies will need to focus on the bioactivity not only of green tea and BT PP but also of their metabolites and biotransformation products.
Article
Green tea catechins (GTCs) exert chemopreventive effects in many cancer models. Several studies implicate the DNA synthesis marker minichromosome maintenance protein 7 (MCM7) in prostate cancer progression, growth and invasion; representing a novel therapeutic target. In this study, we investigated the effect of GTCs on MCM7 expression in the transgenic adenocarcinoma mouse prostate model (TRAMP). DNA microarray, immunohistochemistry and western blot analysis showed that GTCs significantly suppressed MCM7 in the TRAMP mice treated with GTCs. Our study indicates that the cellular DNA replication factor MCM7 is involved in prostate cancer (CaP) and MCM7 gene expression was reduced by GTCs. Together, these results suggest a possible role of GTCs in CaP chemoprevention in which MCM7 plays a critical role.
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Androgens not only play an important role in the development and function of the prostate but they are also intimately involved in the development and progression of prostate cancer (PCa). Within the prostate, testosterone is converted to the more potent androgen dihydrotestosterone (DHT) via the action of 5α-reductase enzymes. DHT is the primary prostatic androgen and promotes the growth and survival of normal, hyperplastic and malignant prostate tissues. Throughout the different stages of PCa [prostatic intraepithelial neoplasia (PIN), localised, recurrent, and metastatic] there is an increase in expression of 5α-reductase enzymes, particularly in localised high-grade carcinoma. Specifically inhibiting 5α-reductase may reduce the production of DHT in the prostate while maintaining other endogenous hormone levels. Clinical studies have shown significant PCa risk reduction by blocking this pathway with 5α-reductase inhibitors (5ARIs). However, this comes at a risk, albeit low, with sexual side effects, gynaecomastia and cardiac failure. In addition, one study has shown a slight, but significant, risk of high-grade PCa. The currently available evidence does not support the routine use of 5α-reductase inhibitors to prevent PCa in the general population. It could, however, be considered as an individual option for high-risk or concerned patients with appropriate education from the prescribing provider.
Article
The incidence of prostate cancer, while still lower than in Western nations, is increasing rapidly in Asian countries due to a more westernized lifestyle. Prostate cancer mortality is declining in the USA, where most prostate cancers are diagnosed in the early stage. In contrast, the mortality rates of prostate cancer in Asian countries are expected to continue to increase, because the percentage of advanced-stage prostate cancers remains high. Therefore, early detection by prostate-specific antigen screening and a comprehensive strategy for cancer prevention are essential for Asian people. The exposure rate of prostate-specific antigen screening is very low in Asian countries. Increased prostate-specific antigen screening may reduce the mortality rate. The stances regarding population screening differ among countries. Urological associations should promote population screening. Reliable data from Asian countries are needed. The prostate cancer incidence is low in Asian countries, perhaps due to high soy consumption. Isoflavones may prevent prostate cancer in Asian countries, but that is not yet clear. A large, multinational study in Asia is needed to clarify whether or not isoflavone consumption shows efficacy in preventing prostate cancer. Clinical data suggest that hormonal therapy is more effective in Asians than in Westerners. Clinical guidelines should consider including hormonal therapy as one of the options for the treatment of localized prostate cancer. At the same time, effort should be made to decrease the adverse effects of each treatment. Collaborative studies on the treatment of prostate cancer should be carried out among Asian countries.
Article
Chronic inflammation and nuclear factor-kappa B (NFκB) have been implicated in prostate cancer development; thus, dietary factors that inhibit NFκB may serve as effective chemo-preventative agents. Prostate cancer risk is significantly lower in Asian countries compared to the United States, which has prompted interest in the potential chemopreventative action of Asian dietary components such as soy and green tea. This study examined the effects of dietary soy and tea on NFκB activation and inflammation in vivo using a hormone-induced rat model for prostate cancer. Male Noble rats implanted with estradiol and testosterone were divided into 4 dietary groups: control, soy, tea, or soy+tea. NFκB activation and inflammatory cytokines were measured post implantation. The combination of soy and tea suppressed NFκB p50 binding activity and protein levels via induction of IκBα. Soy and tea also decreased prostate inflammatory infiltration, increased Bax/BcL2 ratio and decreased protein expression of tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1β compared to control. Soy and tea attenuated prostate malignancy by decreasing prostate hyperplasia. These effects were not apparent in groups treated with soy or tea alone. The ongoing in vivo studies thus far suggest that combination of foods, such as soy and tea, may inhibit hormone-induced proinflammatory NFκB signals that contribute to prostate cancer development.
Article
Epidemiologic, preclinical, and clinical trials suggest that green tea consumption may prevent prostate cancer through the action of green tea polyphenols including (-)-epigallocatechin-3-gallate (EGCG). To study the metabolism and bioactivity of green tea polyphenols in human prostate tissue, men with clinically localized prostate cancer consumed six cups of green tea (n = 8) daily or water (n = 9) for 3 to 6 weeks before undergoing radical prostatectomy. Using high-performance liquid chromatography, 4''-O-methyl EGCG (4''-MeEGCG) and EGCG were identified in comparable amounts, and (-)-epicatechin-3-gallate was identified in lower amounts in prostatectomy tissue from men consuming green tea (38.9 +/- 19.5, 42.1 +/- 32.4, and 17.8 +/- 10.1 pmol/g tissue, respectively). The majority of EGCG and other green tea polyphenols were not conjugated. Green tea polyphenols were not detected in prostate tissue or urine from men consuming water preoperatively. In the urine of men consuming green tea, 50% to 60% of both (-)-epigallocatechin and (-)-epicatechin were present in methylated form with 4'-O-MeEGC being the major methylated form of (-)-epigallocatechin. When incubated with EGCG, LNCaP prostate cancer cells were able to methylate EGCG to 4''-MeEGCG. The capacity of 4''-MeEGCG to inhibit proliferation and NF-kappaB activation and induce apoptosis in LNCaP cells was decreased significantly compared with EGCG. In summary, methylated and nonmethylated forms of EGCG are detectable in prostate tissue following a short-term green tea intervention, and the methylation status of EGCG may potentially modulate its preventive effect on prostate cancer, possibly based on genetic polymorphisms of catechol O-methyltransferase.
Article
The insulin-like growth factors (IGFs; IGF-1 and IGF-2) play central roles in cell growth, differentiation, survival, transformation and metastasis. The biologic effects of the IGFs are mediated by the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase with homology to the insulin receptor (IR). Dysregulation of the IGF system is well recognized as a key contributor to the progression of multiple cancers, with IGF-1R activation increasing the tumorigenic potential of breast, prostate, lung, colon and head and neck squamous cell carcinoma (HNSCC). Despite this relationship, targeting the IGF-1R has only recently undergone development as a molecular cancer therapeutic. As it has taken hold, we are witnessing a robust increase and interest in targeting the inhibition of IGF-1R signaling. This is accentuated by the list of over 30 drugs, including monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) that are under evaluation as single agents or in combination therapies. The IGF-binding proteins (IGFBPs) represent the third component of the IGF system consisting of a class of six soluble secretory proteins. They represent a unique class of naturally occurring IGF-antagonists that bind to and sequester IGF-1 and IGF-2, inhibiting their access to the IGF-1R. Due to their dual targeting of the IGFs without affecting insulin action, the IGFBPs are an untapped "third" class of IGF-1R inhibitors. In this commentary, we highlight some of the significant aspects of and prospects for targeting the IGF-1R and describe what the future may hold.
Article
Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers (theasinensins [THSNs] and P-2 analogs) were quantified in commercial teas by high-performance liquid chromatography-mass spectrometry. (-)-Epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) homodimers were present at 10 to 43 and 0 to 62 mumol/g leaf, respectively. The EGC-EGCG heterodimers were present at 0 to 79 mumol/g. The potential intestinal absorption of these dimers was assessed using Caco-2 intestinal cells. Catechin monomers and dimers were detected in cells exposed to media containing monomers and preformed dimers. Accumulation of dimers was significantly greater than monomers from test media. Three-hour accumulation of EGC and EGCG was 0.19% to 0.55% and 1.24% to 1.35%, respectively. Comparatively, 3-hour accumulation of the EGC P-2 analog and THSNs C/E was 0.89% +/- 0.28% and 1.53% +/- 0.36%, respectively. Accumulation of P-2 and THSNs A/D was 6.93% +/- 2.1% and 10.1% +/- 3.6%, respectively. The EGCG-EGC heterodimer P-2 analog and THSN B 3-hour accumulation was 4.87% +/- 2.2% and 4.65% +/- 2.8%, respectively. One-hour retention of P-2 and THSNs A/D was 171% +/- 22% and 29.6% +/- 9.3% of accumulated amount, respectively, suggesting intracellular oxidative conversion of THSNs to P-2. These data suggest that catechin dimers present in the gut lumen may be readily absorbed by intestinal epithelium.
Article
The transcription factor nuclear factor kappa B (NFkappaB) is found in nearly all animal cell types. It is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL and microbial antigens, and has been shown to regulate the expression of a number of genes including bcl-2, bcl-xl, cIAP, suvivin, TRAF, COX-2, MMP-9, iNOS and cell cycle-regulatory components. Many carcinogens, inflammatory agents and tumor promoters have been shown to activate NFkappaB, and resulting tumors demonstrate misregulated NFkappaB. Incorrect regulation of NFkappaB has been linked to inflammatory and autoimmune diseases, septic shock, viral infection and improper immune development. Aberrant regulation of NFkappaB is involved in cancer development and progression as well as in drug resistance. Inhibitors of NFkappaB mediate effects potentially leading to antitumor responses or greater sensitivity to the action of antitumor agents. Tools have been developed for the rapid assessment of NFkappaB activity, so in concert with a better understanding of NFkappaB activation mechanisms, many agents capable of suppressing NFkappaB activation have been identified. The present article focuses on the functions of NFkappaB, its role in human cancer and the therapeutic potential and benefit of targeting NFkappaB by natural products in cancer chemoprevention.
Article
Green tea (Camellia sinensis) is rich in catechins, of which (-)-epigallocatechin-3-gallate (EGCG) is the most abundant. Studies in animal models of carcinogenesis have shown that green tea and EGCG can inhibit tumorigenesis during the initiation, promotion and progression stages. Many potential mechanisms have been proposed including both antioxidant and pro-oxidant effects, but questions remain regarding the relevance of these mechanisms to cancer prevention. In the present review, we will discuss the redox chemistry of the tea catechins and the current literature on the antioxidant and pro-oxidative effects of the green tea polyphenols as they relate to cancer prevention. We report that although the catechins are chemical antioxidants which can quench free radical species and chelate transition metals, there is evidence that some of the effects of these compounds may be related to induction of oxidative stress. Such pro-oxidant effects appear to be responsible for the induction of apoptosis in tumor cells. These pro-oxidant effects may also induce endogenous antioxidant systems in normal tissues that offer protection against carcinogenic insult. This review is meant point out understudied areas and stimulate research on the topic with the hope that insights into the mechanisms of cancer preventive activity of tea polyphenols will result.