Antimutagenic and anticarcinogenic activity of tea polyphenols

Tea is the most popular beverage, consumed by over two thirds of the world's population. Tea is processed differently in different parts of the world to give green (20%), black (78%) or oolong tea (2%). Green tea is consumed mostly in Japan and China. The antimutagenic and anticarcinogenic activities of green tea are extensively examined. The chemical components of green and black tea are polyphenols, which include EC, ECG, EGC, EGCG and TFs. This article reviews the epidemiological and experimental studies on the antimutagenicity and anticarcinogenicity of tea extracts and tea polyphenols. In Japan, an epidemiological study showed an inverse relationship between habitual green tea drinking and the standardized mortality rates for cancer. Some cohort studies on Chanoyu (Japanese tea ceremony) women teachers also showed that their mortality ratio including deaths caused by malignant neoplasms were surprisingly low. The antimutagenic activity against various mutagens of tea extracts and polyphenols including ECG and EGCG has been demonstrated in microbial systems (Salmonella typhimurium and Escherichia coli), mammalian cell systems and in vivo animal tests. The anticarcinogenic activity of tea phenols has been shown in experimental animals such as rats and mice, in transplantable tumors, carcinogen-induced tumors in digestive organs, mammary glands, hepatocarcinomas, lung cancers, skin tumors, leukemia, tumor promotion and metastasis. The mechanisms of antimutagenesis and anticarcinogenesis of tea polyphenols suggest that the inhibition of tumors may be due to both extracellular and intracellular mechanisms including the modulation of metabolism, blocking or suppression, modulation of DNA replication and repair effects, promotion, inhibition of invasion and metastasis, and induction of novel mechanisms.     

Anticlastogenic effects of black tea (World blend) and its two active polyphenols theaflavins and thearubigins in vivo in Swiss albino mice.

This study investigated the inhibition of cyclophosphamide (CP) and dimethylbenz(a)anthracene (DMBA) induced genetic damage by black tea (World blend) and its two active polyphenols theaflavins (TF) and thearubigins (TR) in Swiss albino mice as measured by chromosome aberrations (CA) and sister chromatid exchanges (SCE). Three different concentrations (5, 10 and 20%) of tea and a single dose of TF and TR were tested for their anticlastogenic effects against DMBA (50 mg/kg body weight) and CP (20 mg/kg for CA and 10 mg/kg for SCE). A significant decrease in CA was observed in all the three concentrations of tea extract plus DMBA treated groups when compared with the respective DMBA treated group alone. Similarly a significant decrease in CA was observed in all the three concentrations of tea extracts plus CP treated series when compared with the group treated with CP alone. In SCE assay, a significant decrease in SCE was observed in 5, 10 and 20% black tea extract plus CP and 10 and 20% tea extracts plus DMBA treated groups when compared with the CP or DMBA treated group alone. In the single dose of TF and TR treated groups a significant decrease in both CA and SCE was observed in both the TF and TR plus both the carcinogen treated groups when compared with their positive controls. The protective effects of black tea extracts were more significant than that of its two polyphenols. This study indicates that both black tea and its active polyphenols TF and TR have significant anticlastogenic effects in bone marrow cells of mice.     

Cancer chemoprevention by tea polyphenols

Tea is one of the most widely consumed beverages, second only to water. Many experimental researches in laboratory animals demonstrated that tea components had an inhibitory effect on carcinogenesis at a number of organ sites. The inhibitory effects of tea against carcinogenesis have been attributed to the biologic activities of the polyphenol fraction in tea. This review summarizes experimental data on chemopreventive effects of tea polyphenols in various tumor bioassay systems. Many laboratory studies have demonstrated the inhibitory effects of green tea polyphenols, especially (-)-epigallocatechin-3-gallate (EGCG), on carcinogenesis in animals models. The majority of these studies have been conducted in mouse skin tumor models, where tea polyphenols were used either as oral feeding in drinking water or in direct local application. Most studies used 12-O-tetradecanoylphorbol-13-acetate (TPA) or ultraviolet (UV) radiation as the tumor promoter and found anticarcinogenic effects caused by green tea polyphenols. Black tea was also found to be effective, although the activity was weaker than that of green tea in some experiments. Other studies showed that black tea polyphenols-theaflavins exhibited stronger anticarcinogenic activity than did EGCG. Caffeine in tea was also important for tea to prevent tumorigenesis. The molecular mechanisms of the cancer chemopreventive effects of tea polyphenols are not completely understood. They are most likely related to the mechanisms of biochemical actions of tea polyphenols, which include antioxidative activities, modulation of xenobiotic metabolite enzymes and inhibition of tumor promotion. In addition, we have also proposed that tea polyphenols function as cancer chemopreventive agents through modulation of mitotic signal transduction. However, the molecular mechanisms involved in this modulation need further investigation.     

Antimutagenic activity of green tea and black tea extracts studied in a dynamic in vitro gastrointestinal model

An in vitro gastrointestinal model, which simulates the conditions in the human digestive tract, was used to determine potential antimutagenic activity of extracts of black tea and green tea. In this paper, results are presented on the availability for absorption of potential antimutagenic compounds present in tea and on the influence of the food matrix on this activity. Between 60 and 180min after the tea was introduced into the model, antimutagenic activity was recovered from the jejunal compartment by means of dialysis: the dialysate appeared to inhibit the mutagenicity of the food mutagen MeIQx in the direct plate assay with Salmonella typhimurium (Ames test). The maximum inhibition was measured at 2h after the start of the experiment and was comparable for black tea and green tea extract. To determine the influence of food matrices on the antimutagenic activity of tea, the model was loaded with black tea together with milk or a homogenized standard breakfast. The maximum inhibition observed with black tea was reduced by 22, 42 and 78% in the presence of whole milk, semi-skimmed milk, and skimmed milk, respectively. Whole milk and skimmed milk abolished the antimutagenic activity of green tea by more than 90%; for semi-skimmed milk the inhibition was more than 60%. When a homogenized breakfast was added into the model together with the black tea extract, the antimutagenic activity was completely eliminated. When tea and MeIQx were added together into the digestion model, MeIQx mutagenicity was efficiently inhibited, with green tea showing a slightly stronger antimutagenic activity than black tea. In this case, the addition of milk had only a small inhibiting effect on the antimutagenicity.Antioxidant capacity and the concentration of catechins were also measured in the jejunal dialysates. The reduction in antimutagenic activity corresponded with reduction in antioxidant capacity and with a decrease of concentration of three catechins, viz. catechin, epigallocatechin gallate and epigallocatechin. The in vitro gastrointestinal model appears to be a useful tool to study the antimutagenicity of food components.     

Black tea,green tea,and tea polyphenols

Previous studies have shown that tea consumption can impair trace element metabolism, particularly iron status, and increase the risk of anemia in humans and animals. More recently, however, evidence has been accumulating to show that, in animals, consumption of green tea or its polyphenols is associated with a reduction of the incidence and severity of a variety of experimentally induced cancers. In this study we have monitored the growth, trace element status, including hematological parameters of weanling rats given either (1) water, (2) 1% black tea, (3) 1% green, tea, or (4) 0.2% crude green tea extract as their sole drinking fluid while consuming diets containing either adequate or low amounts of iron. With the exception of manaanese, none of the trace elements studied (iron, copper, zinc, and manganese) or the hematological indices measured were affected by the type of beverage supplied, even though the polyphenol extract was shown to chelate metals in vitro and all the animals fed the low iron diet were shown to be anemic. There appeared to be an effect of black and green teas on manganese balance in, both the first and last weeks of the study. A lower level of brain managanese was associated with green tea consumption, and a higher level of this element in the kidneys of animals fed black tea. The results demonstrate that both black and green teas and a green tea polyphenol extract do not represent a risk to animals consuming the beverages as their sole fluid intake with respect to iron availability, although the interactions with manganese deserve further study.     

Protective effects of green tea polyphenols and their major component, (-)-epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells

Green tea polyphenols exert a wide range of biochemical and pharmacological effects, and have been shown to possess antimutagenic and anticarcinogenic properties. Oxidative stress is involved in the pathogenesis of Parkinson's disease. However, although green tea polyphenols may be expected to inhibit the progression of Parkinson's disease on the basis of their known antioxidant activity, this has not previously been established. In the present study, we evaluated the neuroprotective effects of green tea polyphenols in the Parkinson's disease pathological cell model. The results show that the natural antioxidants have significant inhibitory effects against apoptosis induced by oxidative stress. 6-Hydroxydopamine (6-OHDA)-induced apoptosis in catecholaminergic PC12 cells was chosen as the in vitro model of Parkinson's disease in our study. Apoptotic characteristics of PC12 cells were assessed by MTT assay, flow cytometry, fluorescence microscopy and DNA fragmentation. Green tea polyphenols and their major component, EGCG at a concentration of 200 microM, exert significant protective effects against 6-OHDA-induced PC12 cell apoptosis. EGCG is more effective than the mixture of green tea polyphenols. The antioxidant function of green tea polyphenols may account for this neuroprotective effect. The present study supports the notion that green tea polyphenols have the potential to be effective as neuropreventive agents for the treatment of neurodegenerative diseases.     

Therapeutic properties of green tea against environmental insults

Pesticides, smoke, mycotoxins, polychlorinated biphenyls (PCBs), and arsenic are the most common environmental toxins and toxicants to humans. These toxins and toxicants may impact on human health at the molecular (DNA, RNA, or protein), organelle (mitochondria, lysosome, or membranes), cellular (growth inhibition or cell death), tissue, organ, and systemic levels. Formation of reactive radicals, lipid peroxidation, inflammation, genotoxicity, hepatotoxicity, embryotoxicity, neurological alterations, apoptosis, and carcinogenic events are some of the mechanisms mediating the toxic effects of the environmental toxins and toxicants. Green tea, the nonoxidized and nonfermented form of tea that contains several polyphenols, including green tea catechins, exhibits protective effects against these environmental toxins and toxicants in preclinical studies and to a much-limited extent, in clinical trials. The protective effects are collectively mediated by antioxidant, antiinflammatory, antimutagenic, hepatoprotective and neuroprotective, and anticarcinogenic activities. In addition, green tea modulates signaling pathway including NF-κB and ERK pathways, preserves mitochondrial membrane potential, inhibits caspase-3 activity, down-regulates proapoptotic proteins, and induces the phase II detoxifying pathway. The bioavailability and metabolism of green tea and its protective effects against environmental insults induced by pesticides, smoke, mycotoxins, PCBs, and arsenic are reviewed in this paper. Future studies with emphasis on clinical trials should identify biomarkers of green tea intake, examine the mechanisms of action of green tea polyphenols, and investigate potential interactions of green tea with other toxicant-modulating dietary factors.     

Anti-invasive effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), a natural inhibitor of metallo and serine proteases

Several reports have attributed to green tea chemopreventive and therapeutic properties. Epidemiological studies have linked the regular use of green tea to a reduced incidence of breast and colon carcinomas. Tea contains several antioxidants, including polyphenols of the catechin (green tea) and theaflavin (black tea) groups. Green tea derivatives have been shown to act in vitro and in vivo as anti-inflammatory, anti-viral and anti-tumor drugs. Despite the extensive body of data only few studies have investigated the molecular mechanisms underlying these effects. In this brief review we focus on the inhibitory activity of catechins derived from green tea toward proteases involved in tumor invasion.     

Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review

BackgroundThe rapid spread of novel coronavirus called SARS-CoV-2 or nCoV has caused countries all over the world to impose lockdowns and undertake stringent preventive measures. This new positive-sense single-stranded RNA strain of coronavirus spreads through droplets of saliva and nasal discharge.PurposeUS FDA has authorized the emergency use of Remdesivir looking at the increasing number of cases of COVID-19, however there is still no drug approved to treat COVID-19. An alternative way of treatment could be the use of naturally derived molecules with known antiviral properties.MethodWe reviewed the antiviral activities of two polyphenols derived from tea, epigallocatechin-3-gallate (EGCG) from green tea and theaflavins from black tea. Both green tea and black tea polyphenols have been reported to exhibit antiviral activities against various viruses, especially positive-sense single-stranded RNA viruses.ResultsRecent studies have revealed the possible binding sites present on SARS-CoV-2 and studied their interactions with tea polyphenols. EGCG and theaflavins, especially theaflavin-3,3′-digallate (TF3) have shown a significant interaction with the receptors under consideration in this review. Some docking studies further emphasize on the activity of these polyphenols against COVID-19.ConclusionThis review summarizes the available reports and evidences which support the use of tea polyphenols as potential candidates in prophylaxis and treatment of COVID-19.     

Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay.

There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce "artificial" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as "scavenging" the reactive intermediate(s).     

Mechanisms of inhibition of carcinogenesis by tea

Tea (Camellia sinensis) preparations have been shown to inhibit tumorigenesis at the initiation, promotion, and progression stages in different animal models. The anti-proliferative effects of tea polyphenols may be a key mechanism, especially in the NNK-induced lung tumorigenesis model with mice. Studies with cell lines have demonstrated that tea polyphenols inhibit cell proliferation and induce apoptosis. The effective concentrations used in these studies (20-100 microM) are usually higher than those observed in blood and tissues of humans and animals, which are in the low micromolar range. Glucuronide and sulfate conjugated and methylated catechins as well as ring fission products (due to intestinal microflora) have been observed in human plasma and urine. Purified green and black tea polyphenols inhibited the H-ras induced milogen-activated protein kinases, AP-1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among the catechins, both the galloyl structure on the B ring and the gallate moiety are important for the inhibition. Both (-)-epigallocatechin-3-gallate and theaflavin-3,3'-digallate inhibited the phosphorylation of c-jun and p44/42 (ERK 1/2). More mechanistic and human studies in these areas will help us to understand the possible inhibitory action of tea against carcinogenesis in humans.     

Antimutagenic activity of selenium-enriched green tea toward the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline

Both selenium and green tea have been reported to exhibit antigenotoxic and cancer chemopreventive properties. We compared the antimutagenic activities of regular green tea and selenium-enriched green tea obtained from Hubei Province, China, toward the heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the Salmonella assay. Selenium-enriched green tea obtained by foliar application of selenite exhibited concentration-dependent inhibition of IQ-induced mutagenesis in the presence of rat liver S9 and was significantly more effective than regular green tea tested under the same conditions. Analytical studies revealed no major differences in the polyphenol or caffeine content between regular green tea and selenium-enriched green tea, but the latter tea contained approximately 60-fold higher concentrations of selenium compared with regular green tea. The only soluble form of selenium was identified as selenite. The antimutagenic effects of certain individual tea constituents, such as epicatechin gallate and catechin, were enhanced by the addition of selenite to the Salmonella assay. Sodium selenite, sodium selenate, seleno-dl-cysteine, seleno-l-methionine, and l-Se-methylselenocysteine were not antimutagenic toward IQ when tested alone, but augmented significantly the inhibitory potency of green tea. The results suggested an enhancing (“coantimutagenic”) effect of selenium in combination with green tea in vitro, but in vivo studies are needed to assess whether there is a synergistic effect of tea and selenium to protect against heterocyclic amine-induced mutagenesis and carcinogenesis.     

Theaflavin derivatives in black tea and catechin derivatives in green tea inhibit HIV-1 entry by targeting gp41

Theaflavin derivatives and catechin derivatives are the major polyphenols in black tea and green tea, respectively. Several tea polyphenols, especially those with galloyl moiety, can inhibit HIV-1 replication with multiple mechanisms of action. Here we showed that the theaflavin derivatives had more potent anti-HIV-1 activity than catechin derivatives. These tea polyphenols could inhibit HIV-1 entry into target cells by blocking HIV-1 envelope glycoprotein-mediated membrane fusion. The fusion inhibitory activity of the tea polyphenols was correlated with their ability to block the formation of the gp41 six-helix bundle, a fusion-active core conformation. Computer-aided molecular docking analyses indicate that these tea polyphenols, theaflavin-3,3'-digallate (TF3) as an example, may bind to the highly conserved hydrophobic pocket on the surface of the central trimeric coiled coil formed by the N-terminal heptad repeats of gp41. These results indicate that tea, especially black tea, may be used as a source of anti-HIV agents and theaflavin derivatives may be applied as lead compounds for developing HIV-1 entry inhibitors targeting gp41.     

Antimutagenic activity of green tea polyphenols

For centuries green tea has been a widely consumed beverage throughout the world. It is known to contain a number of pharmacologically active compounds. In this study water extracts of green tea (WEGT) and their major constituents, green tea polyphenols (GTP), were examined for antimutagenic activity. WEGT and GTP were found to significantly inhibit the reverse mutation induced by benzo[alpha]pyrene (BP), aflatoxin B1 (AFB1), 2-aminofluorene, and methanol extracts of coal tar pitch in Salmonella typhimurium TA100 and/or TA98 in the presence of a rat-liver microsomal activation system. GTP also inhibited gene forward mutation in V79 cells treated with AFB1 and BP, and also decreased the frequency of sister-chromatid exchanges and chromosomal aberrations in V79 cells treated with AFB1. The addition of GTP during and after nitrosation of methylurea resulted in a dose-dependent inhibition of mutagenicity. Studies to define the mechanism of the antimutagenic activity of GTP suggest that it may affect carcinogen metabolism, DNA adduct formation, the interaction of ultimate carcinogen or the scavenging of free radicals.     

Studies of cocoa tea, a wild tea tree containing theobromine

Camellia ptilophylla Chang is a wild tea tree containing theobromine and is caffeine-flee. Lots of researches have been conducted for its domestication since it was discovered to contain theobromine in its shoots. First, its pharmacological and physiological effects have been studied, demonstrating that it can be used as a new resource of tea as daily and healthy beverage. Cocoa tea differs from traditional tea in that it does not excite the nervous system. Second, various ways of propagation have been investigated, and sexless cutting has been the method adopted currently. Third, through selection and breeding, plantation of cocoa tea can be set up to cultivate new varieties, and cocoa tea of different flavors such as green cocoa tea, oolong cocoa tea, and black cocoa tea can be processed. Thus, cocoa tea will become a choice in the tea market.     

Black tea represents a major source of dietary phenolics among regular tea drinkers

The phenolic composition and antioxidant activities [TEAC, ORAC, FRAP] of consumer brews (1 tea bag in 230 ml for 1 min) of seven different brands of black tea from the British market were investigated. The main phenolic compounds identified were epigallocatechin gallate, four theaflavins, as well as epicatechin gallate, theogallin (tentative assignment), quercetin-3-rutinoside and 4-caffeoyl quinic acid. Thearubigins represented an estimated 75-82% of the total phenolics. Further, polyphenol fractions were in decreasing order theaflavins, flavan-3-ols, flavonols, gallic acids and hydroxycinnamates. On average, a cup of a consumer brew of black tea is providing polyphenols at the level of 262 mg GAE/serving, of which 65 mg were assigned to individual polyphenols. The antioxidant activity of black tea preparations is higher than that of most reported dietary agents on a daily basis. Correlations were observed between the antioxidant activities and the sum of all quantified polyphenols by HPLC analysis as well as with the total phenolics. Treatment of the black tea brew with simulated gastric juice resulted in a significant increase of the identified theaflavins implying a partial cleavage of thearubigins in the environment of the gastric lumen. Therefore, black tea can be considered to be a rich source of polyphenols and/or antioxidants.     

Cellular thiols status and cell death in the effect of green tea polyphenols in Ehrlich ascites tumor cells.

Epidemiological studies suggest that the consumption of green tea may help prevent cancers in humans, and also breast and prostate cancers in animal models are reduced by green tea, and several mechanisms have been proposed for these effects. In this study the relationship between cellular sulfhydryl (SH) groups and the cytotoxicity of green tea polyphenols in Ehrlich ascites tumor cells was examined. It was found that in the presence of green tea extract (GTE) (100 microg/ml) and one of its polyphenolic components, epigallocatechin (EGC; 100 microM), both cellular non-protein (GSH) and protein-sulfhydryl (PSH) levels were significantly decreased and this was associated with a decrease in cell viability. Replenishing the thiol levels by using N-acetylcysteine (NAC) caused a recovery in cell viability, but this recovery was dependent on the time of thiol replenishment in the presence of EGC (initial 15 min). These results identify SH groups as a novel target of green tea polyphenols cytotoxicity in tumor cells, and a regulatory role for green tea in terms of reducing sulfhydryls in tumor inhibition.     

Cancer chemopreventive mechanisms of tea against heterocyclic amine mutagens from cooked meat

Cooking meat and fish under normal conditions produces heterocyclic amine mutagens, several of which have been shown to induce colon tumors in experimental animals. In our search for natural dietary components that might protect against these mutagens, it was found that green tea and black tea inhibit the formation of heterocyclic amine-induced colonic aberrant crypt foci (ACF) in the rat. Since ACF are considered to be putative preneoplastic lesions, we examined the inhibitory mechanisms of tea against the heterocyclic amines. In the initial studies using the Salmonella mutagenicity assay, green tea and black tea inhibited according to the concentration of tea leaves during brewing and the time of brewing; a 2-3-min brew of 5% green tea (w/v) was sufficient for >90% antimutagenic activity. N-hydroxylated heterocyclic amines, which are direct-acting mutagens in Salmonella, were inhibited by complete tea beverage and by individual components of tea, such as epigallocatechin-3-gallate (EGCG). Inhibition did not involve enhanced mutagen degradation, and EGCG and other catechins complexed only weakly with the mutagens, suggesting electrophile scavenging as an alternative mechanism. Enzymes that contribute to the metabolic activation of heterocyclic amines, namely microsomal NADPH-cytochrome P450 reductase and N, O-acetyltransferase, were inhibited by tea in vitro. Studies in vivo established that tea also induces cytochromes P450 and Phase II enzymes in a manner consistent with the rapid metabolism and excretion of heterocyclic amines. Collectively, the results indicate that tea possesses anticarcinogenic activity in the colon, and this most likely involves multiple inhibitory mechanisms.     

Protective effects of green tea polyphenols on human HepG2 cells against oxidative damage of fenofibrate

The aim of this work was to investigate the protective effects of green tea polyphenols on the cytotoxic effects of hypolipidemic agent fenofibrate (FF), a peroxisome proliferator (PP), in human HepG2 cells. The results showed that high concentrations of FF induced human HepG2 cell death through a mechanism involving an increase of reactive oxygen species (ROS) and intracellular reduced glutathione (GSH) depletion. These effects were partially prevented by antioxidant green tea polyphenols. The elevated expression of PP-activated receptors alpha (PPARalpha) in HepG2 cells induced by FF was also decreased by treatment with green tea polyphenols. In conclusion, this result demonstrates that oxidative stress and PPARalpha are involved in FF cytotoxicity and green tea polyphenols have a protective effect against FF-induced cellular injury. It may be beneficial for the hyperlipidemic patients who were administered the hypolipidemic drug fenofibrate to drink tea or use green tea polyphenols synchronously during their treatment.     

In vitro evaluation of the anticancer effect of lactoferrin and tea polyphenol combination on oral carcinoma cells

We investigated the anticancer effects of green and black tea polyphenols alone and in combination with bovine milk lactoferrin (bLF) on human tongue squamous carcinoma (CAL-27) and normal human gingival fibroblast (HGF) cells. Both green (Polyphenon-E;P-E) and black tea polyphenols (Polyphenon-B;P-B) preferentially inhibit the growth of CAL-27 cells in a dose-dependent manner. Based on the IC(50) values, P-E was found to be more effective than P-B and the combination of P-E and bLF (1:2 ratio) exhibited synergistic inhibition of CAL-27 cells. Analysis of the mechanism revealed nuclear fragmentation and condensation with appearance of the A(o) peak indicative of apoptosis. Furthermore, tea polyphenols transduced the apoptosis signal via generation of reactive oxygen species and decrease in the Bcl-2/Bax ratio thereby inducing mitochondrial permeability transition with consequent activation of caspase-3. Overall, the potency of cytotoxic and apoptosis inducing effects of dietary agents on CAL-27 cells was in the order P-E and bLF combination (1:2 ratio)>P-E>P-B. These results suggest that a "designer" approach may be useful for oral cancer prevention strategies.