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PubMed1999

Effects of tea polyphenols on the invasion and matrix metalloproteinases activities of human fibrosarcoma HT1080 cells.

The effects of tea polyphenols on the invasion of highly metastatic human fibrosarcoma HT1080 cells through a monolayer of human umbilical vein endothelial cells (HUVECs) and the accompanying basal membrane were investigated. Among the tea polyphenols tested, epicatechin gallate (ECg), epigallocatechin gallate (EGCg), and theaflavin strongly suppressed the invasion of HT1080 cells into the monolayer of HUVECs/gelatin membrane, whereas epicatechin, epigallocatechin, tea flavonols, tea flavones, and gallate derivatives had no effect. Both theaflavin-digallate and theasinensin D showed a weak invasion inhibitory effect. ECg significantly inhibited the invasion without cytotoxicity against cancer cells and HUVECs. Ester-type catechins (ECg and EGCg) and theaflavin strongly suppressed the gelatin degradation mediated by matrix metalloproteinase (MMP) 2 and MMP-9, which were secreted into the conditioned medium of HT1080 cells. In conclusion, among the tea polyphenols tested, ECg was considered to be the agent with the most potential antimetastasis activity because it inhibited invasion in the absence of cytotoxicity.

Antioxidants↗
PubMed2000

Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals.

Mitochondrial proton F0F1-ATPase/ATP synthase synthesizes ATP during oxidative phosphorylation. In this study, we examined the effects of several groups of polyphenolic phytochemicals on the activity of the enzyme. Resveratrol, a stilbene phytoalexin that is present in grapes and red wine, concentration-dependently inhibited the enzymatic activity of both rat brain and liver F0F1-ATPase/ATP synthase (IC(50) of 12 - 28 microM). Screening of other polyphenolic phytochemicals using rat brain F0F1-ATPase activity resulted in the following ranking potency (IC(50) in parenthesis): piceatannol (8 microM)>resveratrol (19 microM)=(-)epigallocatechin gallate (17 microM)>(-)epicatechin gallate, curcumin (45 microM)>genistein=biochanin A=quercetin=kaempferol=morin (55 - 65 microM)>phloretin=apigenin=daidzein (approx. 100 microM). Genistin, quercitrin, phloridzin, (+)catechin, (+)epicatechin, (-)epicatechin and (-)epigallocatechin had little effect at similar concentrations. Tannic acid, theaflavins (tea extract) and grape seed proanthocyanidin extract (GSPE) had IC(50) values of 5, 20 and 30 microg ml(-1), respectively. Several monophenolic antioxidants and non-phenolic compounds were ineffective at concentrations of 210 microM or higher. The inhibition of F0F1-ATPase by resveratrol and genistein was non-competitive in nature. The effects of polyphenolic phytochemicals were additive. Both resveratrol and genistein had little effect on the Na(+)/K(+)-ATPase activity of porcine cerebral cortex, whereas quercetin had similar inhibitory potency as for F0F1-ATPase. In conclusion, the ATP synthase is a target for dietary phytochemicals. This pharmacological property of these phytochemicals should be included in the examination of their health benefits as well as potential cytotoxicity.

Animals↗
PubMed2001

Simultaneous (or sequential) determination of the total polyphenol index (or I280) and density in wines by flow injection.

Flow injection methods for the determination of the total polyphenol index, the 'index 280' (I280) and dissolved solids in wines are proposed. The determination of the total polyphenol index is based on the Folin-Ciocalteu reaction in a basic medium and subsequent spectrophotometric detection at 750 nm. The direct measurement at 280 nm of the wine allows the determination of I280 with a simple manifold. The dissolved solids determination is based on the displacement of a light beam when the refractive index of the medium changes. This phenomenon, followed by a change in the absorbance in a photometric detector, usually takes place when an injected sample reaches the flow cell, and it is magnified on passage of the light beam in the radial direction instead of the more common axial direction. The use of a capillary (4 cm x 1.1 mm id) as the flow cell allows monitoring of the injected plug. A simple manifold coupled with a diode array spectrophotometer allows the determination of these parameters with a frequency of at least 90 h-1. Depending of the method adopted for the determination of polyphenols, Folin-Ciocalteu or I280, either a manifold different from that used for determining dissolved solids or the same, respectively, is required. The methods have been successfully applied to different wines and were substantiated well with official methods.

Journal Article↗
PubMed2001

Amine oxidase-like activity of polyphenols. Mechanism and properties.

Polyphenols in several oxidation systems gained amine oxidase-like activity, probably due to the formation of the corresponding quinones. In the presence of Cu(II), o- and p-phenolic compounds exhibited amine oxidase-like activity, whereas only the o-phenolic compounds showed the activity in the presence of 1,1-diphenyl-2-picrylhydrazyl radical. The activity was determined by measuring the conversion of benzylamine to benzaldehyde by HPLC. Moreover, gallic acid, chlorogenic acid, and caffeic acid, which are plant polyphenols, converted the lysine residue of bovine serum albumin to alpha-amino-adipic semialdehyde residue, indicating lysyl oxidase-like activity. We also characterized the activity of pyrocatechol, hydroquinone, and pyrogallol in the presence of Cu(II). The oxidative deamination was accelerated at a higher pH, and required O2 and transition metal ions. Furthermore, EDTA markedly inhibited the reaction but not beta-aminopropionitrile, which is a specific inhibitor of lysyl oxidase. Catalase significantly inhibited the oxidation, implying the participation of hydroxyl radical in the reaction, but superoxide dismutase stimulated the oxidation, probably due to its radical formation activity. We discussed the mechanism of the oxidative deamination by polyphenols and the possible significance of the activity for biological systems.

Amine Oxidase (Copper-Containing)↗
PubMed2001

The molecular interaction of human salivary histatins with polyphenolic compounds.

Dietary tannins are polyphenols that are effectively precipitated by salivary histatins (Hsts), a novel family of tannin binding proteins. Epigallocatechin gallate (EGCG), a flavan-3-ol ester related to condensed tannins (polymerized products of flavan-3-ols), and pentagalloyl glucose (PGG), a hydrolyzable tannin, were used to evaluate the molecular nature of Hst-polyphenol interaction. NMR demonstrated that Hst5, a representative Hst, bound to EGCG in a hydrophobic manner via basic and aromatic residues. In contrast, proline plays a dominant role in polyphenol binding to other tannin precipitating proteins. The role of basic and aromatic amino acids in EGCG binding was investigated using a series of modified Hsts in each of which one type of amino acid was substituted by Ala. EGCG bound to all modified Hsts, but the binding was diminished. Optimal EGCG binding also depended on the primary structure, as a polypeptide with randomised Hst5 sequence showed significantly diminished interaction with EGCG. Soluble EGCG/Hst5 complexes containing up to seven molecules of EGCG per mol of Hst5 had a 1-mM dissociation constant. In contrast to EGCG, PGG formed small soluble complexes with Hst5 consisting of only one molecule each of PGG and Hst5, as demonstrated by analytical ultracentrifugation. These complexes became insoluble upon binding of additional molecules of PGG. Diminished PGG binding was seen to a peptide with a Hst5 randomized sequence showing the importance of the primary structure. Hsts may serve to form insoluble complexes with tannins thereby preventing their absorption from the intestines and potentially harmful biological effects. In contrast the much weaker interaction with EGCG may allow its uptake into the organism and exploitation of its antioxidant effect.

Amino Acid Sequence↗
PubMed1994

Degradation of polyphenols (catechin and tannic acid) in the rat intestinal tract. Effect on colonic fermentation and faecal output.

Low- and intermediate-molecular-weight polyphenols are usually extracted by using different solvents (e.g. water, methanol, aqueous acetone). The aim of the present work was to study the possible effects of some extractable polyphenols (EPP) on fat and protein digestibilities and on the colonic microflora. Degradability of these compounds through the intestinal tract was also studied. Catechin and tannic acid (TA) were chosen as representatives of the most common basic structures of EPP (flavonoids and gallic acid respectively). Three groups of eight male Wistar rats were given either a control diet free of EPP, or diets containing 20 g/kg dry matter of catechin and TA. Body-weight and food intake were monitored during a 3-week experimental period. Faeces and urine were collected daily during the third experimental week. EPP and fat were determined in faeces, and N in both urine and faeces. Only 3.1 and 4.6% of the ingested catechin and TA respectively were excreted in faeces, indicating that absorption and/or degradation of these EPP had occurred. HPLC analysis of the polyphenolic content of faeces showed qualitative differences between groups. A significant increase of total faecal weight as well as water, fat and N excretion was produced by TA. Catechin only caused an increase in fat excretion. In vitro fermentation assays were also performed to study the effect of EPP on the colonic microflora. Both catechin and TA affected the yield of end-products of fermentation, and were also degraded during the fermentation process.

Animals↗
PubMed2001

NMR and simulated annealing investigations of bradykinin in presence of polyphenols.

Epidemiological studies have shown that the incidence of some cardiovascular degenerative diseases appears to be lower in populations with regular but moderate drinking of red wine rich in polyphenols. One of the most important properties of polyphenols is to form complexes with proteins. The linear nonapeptide hormone bradykinin (H-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9-OH) is involved in a variety of physiological processes such as the cardiovascular processes. Thus, the goal of this work was to study the effects of tannins on the peptide structure by NMR investigations and molecular modeling. The results of these investigations show that in the presence of catechin, the peptide conformation is not affected and is in a random coil structure. On the contrary, the peptide structure is modified by the addition of dimeric proanthocyanidin B3 (catechin 4alpha-->8 catechin). The dimer leads to the formation of a large flexible turn between the 6-9 residues. Thus, the biological activities of bradykinin in the presence of polyphenols could be affected.

Anthocyanins↗
PubMed1981

Polyphenol oxidase and peroxidase in fruits and vegetables.

Polyphenol oxidases and peroxidases are among the most studied enzymes in fruits and vegetables. Owing to the deleterious effects of discoloration and off-flavor formation induced by their actions, these enzymes have not ceased to be a matter of concern to food technologists, while their versatility as catalyst and their diversity as protein present a challenge to the biochemist. This article gives an account on the present state of knowledge in this field. The occurrence of polyphenol oxidases and peroxidases in food and food raw materials, and their role and importance in food processing are briefly outlined. Results of biochemical research including catalytic properties, substrate specificity, susceptibility towards pH and temperature, action of inhibitors, isolation, purification, and characteristics of the enzymes are given, with special emphasis on recent achievements based on high resolution separation and isoenzyme techniques. Finally, the behavior of polyphenol oxidase and peroxidase in selected major groups of fruits and vegetables is discussed. Some contradictions found in the literature are pointed out and some questions that have not been given the necessary attention by researchers so far are mentioned.

Basidiomycota↗
PubMed2005

Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations.

Many plant polyphenolic compounds have been shown to have cancer-preventing activities in laboratory studies. For example, tea and tea preparations have been shown to inhibit tumorigenesis in a variety of animal models of carcinogenesis, involving organ sites such as the skin, lungs, oral cavity, esophagus, stomach, liver, pancreas, small intestine, colon, and prostate. In some of these models, inhibitory activity was demonstrated when tea was administered during the initiation, promotion, or progression stage of carcinogenesis. The cancer-preventing activities of these and other polyphenols, such as curcumin, genistein, and quercetin, are reviewed. In studies in vitro, many of these compounds have been shown to affect signal transduction pathways, leading to inhibition of cell growth and transformation, enhanced apoptosis, reduced invasive behavior, and slowed angiogenesis. However, the concentrations used in cell culture studies were much higher than those found in vivo. If we propose mechanisms for cancer prevention on the basis of cell line experiments, then these activities must be demonstrated in vivo. The bioavailability, ie, tissue and cellular concentrations, of dietary polyphenols is a determining factor in their cancer-preventing activity in vivo. For example, compounds such as curcumin are effective when applied topically to the skin or administered orally to affect the colon but are not effective in internal organs such as the lungs. More in-depth studies on bioavailability should facilitate correlation of mechanisms determined in vitro with in vivo situations, increase our understanding of dose-response relationships, and facilitate extrapolation of results from animal studies to human situations.

Animals↗
PubMed2003

Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin.

The use of botanical supplements has received immense interest in recent years to protect human skin from adverse biological effects of solar ultraviolet (UV) radiation. The polyphenols from green tea are one of them and have been shown to prevent photocarcinogenesis in animal models but their mechanism of photoprotection is not well understood. To determine the mechanism of photoprotection in in vivo mouse model, topical treatment of polyphenols from green tea (GTP) or its most chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) (1 mg/cm(2) skin area) in hydrophilic ointment USP before single (180 mJ/cm(2)) or multiple UVB exposures (180 mJ/cm(2), daily for 10 days) resulted in significant prevention of UVB-induced depletion of antioxidant enzymes such as glutathione peroxidase (78-100%, P < 0.005-0.001), catalase (51-92%, P < 0.001) and glutathione level (87-100%, P < 0.005). Treatment of EGCG or GTP also inhibited UVB-induced oxidative stress when measured in terms of lipid peroxidation (76-95%, P < 0.001), and protein oxidation (67-75%, P > 0.001). Further, to delineate the inhibition of UVB-induced oxidative stress with cell signaling pathways, treatment of EGCG to mouse skin resulted in marked inhibition of a single UVB irradiation-induced phosphorylation of ERK1/2 (16-95%), JNK (46-100%) and p38 (100%) proteins of MAPK family in a time-dependent manner. Identical photoprotective effects of EGCG or GTP were also observed against multiple UVB irradiation-induced phosphorylation of the proteins of MAPK family in vivo mouse skin. Photoprotective efficacy of GTP given in drinking water (d.w.) (0.2%, w/v) was also determined and compared with that of topical treatment of EGCG and GTP. Treatment of GTP in d.w. also significantly prevented single or multiple UVB irradiation-induced depletion of antioxidant enzymes (44-61%, P < 0.01-0.001), oxidative stress (33-71%, P < 0.01) and phosphorylation of ERK1/2, JNK and p38 proteins of MAPK family but the photoprotective efficacy was comparatively less than that of topical treatments of EGCG and GTP. Lesser photoprotective efficacy of GTP in d.w. in comparison with topical application may be due to its less bioavailability in skin target cells. Together, for the first time a cream based formulation of green tea polyphenols was tested in this study to explore the possibility of its use for the humans, and the data obtained from this in vivo study further suggest that GTP could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans.

Animals↗
PubMed2006

Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates.

By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n = 9 per beverage) and on isolated rat aortic rings (n = 9). Healthy males randomly consumed each beverage in a cross-over design. Plasma ethanol, catechin, and urate concentrations were measured before and 30, 60 and 120 minutes after beverage intake. Endothelial function was assessed before and 60 minutes after beverage consumption by normalized flow-mediated dilation (FMD). RW and DARW induced similar vasodilatation in the isolated vessels whereas PSRW, ET, and W did not. All ethanol-containing beverages induced similar basal vasodilatation of brachial artery. Only intake of RW resulted in enhancement of endothelial response, despite similar plasma catechin concentration after DARW. The borderline effect of RW on FMD (P = 0.0531) became significant after FMD normalization (P = 0.0043) that neutralized blunting effect of ethanol-induced basal vasodilatation. Effects of PSRW and ET did not differ although plasma urate increased after PSRW and not after ET, indicating lack of urate influence on endothelial response. Acute vascular effects of RW, mediated by polyphenols, cannot be predicted by plasma catechin concentration only.

Adult↗
PubMed1970

Studies on Auxin Protectors: IX. Inactivation of Certain Protectors by Polyphenol Oxidase.

Protector-II (Pr-II) of the Japanese morning glory (Pharbitis nil Choisy) was inactivated by exposure to polyphenol oxidase. An unidentified protector in the same molecular weight range obtained from sunflower was also inactivated by this enzyme. Earlier speculations that protectors might be lipoprotein in nature were negated by the fact that neither lipase nor protease inactivated the protectors. The protectors were also not inactivated by incubating with alpha-amylase, DNase, or RNase. Catechol mimics Pr and is inactivated by polyphenol oxidase. The oxidation of catechol to o-quinone is accompanied by a loss of chromophores that absorb ultraviolet light and the appearance of a reddish brown color. Similarly, when the relatively low molecular weight auxin protectors (Pr-II class) were incubated with polyphenol oxidase, their oxidation was also frequently associated with the formation of brown color, and oxidation with H(2)O(2) caused a loss of ultraviolet-absorbing chromophores. The data indicate that auxin protectors contain o-dihydroxyphenolic groups at their active site.That o-dihydroxyphenols inhibit indoleacetic acid oxidation has been demonstrated by numerous workers. It is suggested that the high molecular weight auxin protectors and the phenolic compounds described by other authors comprise part of a metabolic system concerned with the regulation of peroxidase-catalyzed redox reactions.

Journal Article↗
PubMed1971

Effect of Phloroglucinol and Resorcinol on the Clingstone Peach Polyphenol Oxidase-catalyzed Oxidation of 4-Methylcatechol.

Phloroglucinol and resorcinol are not substrates for clingstone peach (Prunus persica) polyphenol oxidase, but they react with 4-methyl-o-quinone, produced either enzymatically or nonenzymatically, to give an intense red or red-brown color with a maximal absorption at about 470 nanometers. Several colored products were isolated from an ethyl acetate extract of the reaction by two-dimensional thin layer chromatography. Based on thin layer chromatographic and spectral studies of the enzymatic and nonenzymatic reactions, polyphenol oxidase does not play a role in the reaction between 4-methyl-o-quinone and phloroglucinol, resorcinol, d-catechin, or orcinol. In such reactions, the function of polyphenol oxidase is the formation of 4-methyl-o-quinone which then reacts nonenzymatically with the above phenols. Activation energies of both enzymatic and nonenzymatic reactions were determined.

Journal Article↗
PubMed1973

Changes in Amount of Polyphenols and Activity of Related Enzymes during Growth of Tobacco Flower and Capsule.

Developmental stages of tobacco (Nicotiana tabacum L. cv. Burley 21) flower and capsule were correlated with tissue contents of polyphenols and activities of phenylalanine ammonialyase, polyphenoloxidase, and peroxidase. Chlorogenic acid, scopolin, and scopoletin were present in most tissues, whereas rutin and two dihydroxyphenolic glycosides concentrated primarily in the corolla and placenta, respectively. Ovules contained only chlorogenic acid. As development progressed, polyphenols accounted for nearly 15% of the dry weight in the green capsule of field-grown plants. Fertilization triggered a rapid increase of chlorogenic acid in the ovary. When l-phenylalanine-U-(14)C was fed to the detached green capsules and capsule parts, an incorporation of radioactivity into chlorogenic acid and dihydroxyphenolic glycosides occurred which suggested in situ synthesis of these compounds. This was subtantiated by a positive correlation between phenylalanine ammonia-lyase activity and polyphenol accumulation. High polyphenoloxidase activity was associated mainly with the ovary, whereas peroxidase activity was maximal during senescence of all tissues. Polyacrylamide gel slab electrophoresis revealed five cathodic bands and one diffuse zone with poly-phenoloxidase activity in flower extracts. Two anodic poly-phenoloxidase isozymes appeared only in the fertilized ovary. Among 17 peroxidase isozymes, six cathodic forms were present throughout floral development, and the anodic ones increased in number and activity at the later stages of capsule growth.

Journal Article↗
PubMed1979

Soluble polyvinylpyrrolidine and bovine serum albumin adsorb polyphenols from soybean suspension cultures.

Soybean (Glycine max [L.] Merrill, cv. Dare) suspension cultures grown in Gamborg B5 medium became discolored and the cells began aggregating after 1 week in culture, especially in the absence of 2,4-dichlorophenoxyacetic acid (2,4-D). The addition of either soluble polyvinylpyrrolidine (PVP) or bovine serum albumin (BSA) to cultures grown in Gamborg B5 medium with 2,4-D prevents discoloration and cell aggregation by adsorbing excess polyphenols from the cells. Transfer of the PVP-treated cultures to fresh medium without 2,4-D stimulated the recurrence of excess polyphenols. Cultures pretreated with BSA did not develop excess polyphenols when transferred to fresh 2,4-D-free medium. Addition of either PVP or BSA to cultures grown in the absence of 2,4-D was found to inhibit growth.

Journal Article↗
PubMed1980

Ribulose-1,5-bisphosphate Carboxylase/Oxygenase and Polyphenol Oxidase in the Tobacco Mutant Su/su and Three Green Revertant Plants.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) was crystallized from a heterozygous tobacco (Nicotiana tabacum L.) aurea mutant (Su/su), its wild-type sibling (su/su), and green revertant plants regenerated from green spots found on leaves of haploid Su plants. No differences were found in the specific activity or kinetic parameters of this enzyme, when comparing Su/su and su/su plants of the same age, which had been grown under identical conditions. The enzyme crystallized from revertant plants was also identical to the enzyme from wild-type plants with the exception of one clone, designated R2. R2 has a chromosome number approximately double that of the wild-type (87.0 +/- 11.1 versus 48). The enzyme from R2 had a lower V(max) for CO(2), although the K(m) values were identical to those for the enzyme from the wild-type plant. The enzyme from all mutant plants had identical isoelectric points, identical molecular weight as demonstrated by migration on native and sodium dodecyl sulfate (SDS)-polyacrylamide gels, and the same ratio of large to small subunits as the enzyme from the wild-type. The large subunit of the enzyme from tobacco leaves exhibited a different electrophoretic pattern than did the large subunit from spinach; there were two to three bands on SDS-polyacrylamide gels for the tobacco enzyme whereas the enzyme from spinach had only one species of large subunit.Total polyphenol oxidase activity was the same in leaves from the heterozygous mutant (Su/su) and wild-type (su/su) plants when correlated with developmental age as represented by morphology rather than by the chronological age of the plants. There was a marked increase in the soluble activity of this enzyme with increasing age of both plant types and also as a result of varying environmental conditions. Ribulose-1,5-bisphosphate carboxylase/oxygenase activity correlated inversely with increases in the soluble activity of polyphenol oxidase in crude homogenates from which the carboxylase/oxygenase was crystallized over a generation of Su/su and su/su plants. Criteria are outlined for determining if differences in activity of ribulose-1,5-bisphosphate carboxylase/oxygenase are caused by an effect of polyphenol oxidase activity and/or by some other extrinsic parameter.

Journal Article↗
PubMed1991

Wound-induced deposition of polyphenols in transgenic plants overexpressing peroxidase.

Tobacco (Nicotiana tabacum) plants transformed with a chimeric tobacco anionic peroxidase gene have previously been shown to synthesize high levels of peroxidase in all tissues throughout the plant. One of several distinguishable phenotypes of transformed plants is the rapid browning of pith tissue upon wounding. Pith tissue from plants expressing high levels of peroxidase browned within 24 hours of wounding, while tissue from control plants did not brown as late as 7 days after wounding. A correlation between peroxidase activity and wound-induced browning was observed, whereas no relationship between polyphenol oxidase activity and browning was found. The purified tobacco anionic peroxidase was subjected to kinetic analysis with substrates which resemble the precursors of lignin or polyphenolic acid. The purified enzyme was found to readily polymerize phenolic acids in the presence of H(2)O(2) via a modified ping-pong mechanism. The percentage of lignin and lignin-related polymers in cell walls was nearly twofold greater in pith tissue isolated from peroxidase-overproducer plants compared to control plants. Lignin deposition in wounded pith tissue from control plants closely followed the induction of peroxidase activity. However, wound-induced lignification occurred 24 to 48 hours sooner in plants overexpressing the anionic peroxidase. This suggests that the availability of peroxidase rather than substrate may delay polyphenol deposition in wounded tissue.

Journal Article↗
PubMed1997

Mechanisms of growth inhibition of human lung cancer cell line, PC-9, by tea polyphenols.

(-)-Epigallocatechin gallate (EGCG), the main constituent of green tea, and green tea extract show growth inhibition of various cancer cell lines, such as lung, mammary, and stomach. We studied how tea polyphenols induce growth inhibition of cancer cells. Since green tea extract contains various tea polyphenols, such as EGCG, (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC), the inhibitory potential of each tea polyphenol on the growth of a human lung cancer cell line, PC-9 cells, was first examined. EGC and ECG inhibited the growth of PC-9 cells as potently as did EGCG, but EC did not show significant growth inhibition. The mechanism of growth inhibition by EGCG was studied in relation to cell cycle regulation. Flow cytometric analysis revealed that treatment with 50 microM and 100 microM EGCG increased the percentages of cells in the G2-M phase from 13.8% to 15.6% and 24.1%, respectively. The DNA histogram after treatment with 100 microM EGCG was similar to that after treatment with genistein, suggesting that EGCG induces G2-M arrest in PC-9 cells. Moreover, we found by microautoradiography that [3H]EGCG was incorporated into the cytosol, as well as the nuclei. These results provide new insights into the mechanisms of action of EGCG and green tea extract as cancer-preventive agents in humans.

Antineoplastic Agents↗