Ge-Regulated Ordered Phase in Pseudosphere-Structured LiNi0.5Mn1.5O4 Spinel Effectively Inhibits Mn Dissolution.

Due to the higher energy density, high thermal stability, and low cost, LiNi0.5Mn1.5O4 (LNMO) spinel, with a large voltage operating window, has been one of the most promising cathode materials for lithium-ion batteries (LIBs). However, the interfacial reaction between the cathode and electrolyte and the two-phase reaction within the bulk of LNMO would destroy the original structure and lead to capacity deterioration, posing a significant challenge. Therefore, the way to suppress the transition-metal (TM) dissolution in LNMO has attracted much attention. However, the ordered/disordered phase regulation by metal atom doping to prohibit TM dissolution has not been extensively explored. Herein, a Ge-doping strategy is proposed to adjust the ratio of disordered/ordered phases in LNMO, resulting in exceptional structural stability. For the modified spinel cathode, there is almost no voltage drop and the capacity retention is up to 92.2% over 1000 cycles at 1C. These results demonstrate that incorporating Ge into LNMO forms a robust structure that effectively increases the amount of Mn4+ while blocking the diffusion of TM ions. In addition, Ge-doping also protects the bulk from further reactions with electrolytes, significantly enhancing the interfacial stability and relieving voltage decay in cycling. This approach can also be applied to design other high-stability cathodes through ordered/disordered phase regulation.

Compressive Mechanical Properties and Shock-Induced Reaction Behavior of Zr/PTFE and Ti/PTFE Reactive Materials.

Existing research on PTFE-based reactive materials (RMs) mostly focuses on Al/PTFE RMs. To explore further possibilities of formulation, the reactive metal components in the RMs can be replaced. In this paper, Zr/PTFE and Ti/PTFE RMs were prepared by cold isostatic pressing and vacuum sintering. The static and dynamic compressive mechanical properties of Zr/PTFE and Ti/PTFE RMs were investigated at different strain rates. The results show that the introduction of zirconium powder and titanium powder can increase the strength of the material under dynamic loading. Meanwhile, a modified J-C model considering strain and strain rate coupling was proposed. The parameters of the modified J-C model of Zr/PTFE and Ti/PTFE RMs were determined, which can describe and predict plastic flow stress. To characterize the impact-induced reaction behavior of Zr/PTFE and Ti/PTFE RMs, a quasi-sealed test chamber was used to measure the over-pressure induced by the exothermic reaction. The energy release characteristics of both materials were more intense under the higher impact.

Surface Engineering and Trace Cobalt Doping Suppress Overall Li/Ni Mixing of Li-rich Mn-based Cathode Materials.

To supress Li/Ni mixing, the strategy of surface modification and Co doping is proposed. Doping trace Co can suppress Li/Ni mixing in the bulk phase of cathode particles, while the rock-salt shell of a cathode originally containing a large amount of Li/Ni mixed rows can be transformed into a cation-ordered spinel phase and a layered phase on the inside by means of surface engineering. Simultaneously, as a coating layer, the Li2MoO4 nanolayer forms on the surface. With the improved Li-ion diffusion, certain inhibitory effects on voltage attenuation and capacity loss are found. It shows that the surface modification with trace Co dopants greatly reduces the Li/Ni mixing level in the material, beneficial to improving the electrochemical performance. As expected, the Li-rich Mn-based cathode material with a low level of overall Li/Ni mixing shows an initial discharging capacity of 303 mAh g-1. This indicates that the joint application of doping and surface coating effectively enhances the performance of the cathode materials with an ultra-low dosage of Co. This idea is helpful to structure other layered cathode materials by surface engineering.

Regulating effect of ß-ketoacyl synthase domain of fatty acid synthase on fatty acyl chain length in de novo fatty acid synthesis.

Fatty acid synthase (FAS) is a multifunctional homodimeric protein, and is the key enzyme required for the anabolic conversion of dietary carbohydrates to fatty acids. FAS synthesizes long-chain fatty acids from three substrates: acetyl-CoA as a primer, malonyl-CoA as a 2 carbon donor, and NADPH for reduction. The entire reaction is composed of numerous sequential steps, each catalyzed by a specific functional domain of the enzyme. FAS comprises seven different functional domains, among which the ß-ketoacyl synthase (KS) domain carries out the key condensation reaction to elongate the length of fatty acid chain. Acyl tail length controlled fatty acid synthesis in eukaryotes is a classic example of how a chain building multienzyme works. Different hypotheses have been put forward to explain how those sub-units of FAS are orchestrated to produce fatty acids with proper molecular weight. In the present study, molecular dynamic simulation based binding free energy calculation and access tunnels analysis showed that the C16 acyl tail fatty acid, the major product of FAS, fits to the active site on KS domain better than any other substrates. These simulations supported a new hypothesis about the mechanism of fatty acid production ratio: the geometric shape of active site on KS domain might play a determinate role.

Potent Inhibitory Effect of Chinese Dietary Spices on Fatty Acid Synthase.

Dietary spices have been adopted in cooking since ancient times to enhance flavor and also as food preservatives and disease remedies. In China, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their functions. Fatty acid synthase (FAS) has been recognized as a remedy target, and its inhibitors might be applied in disease treatment. The present work was designed to assess the inhibitory activities on FAS of spices extracts in Chinese menu. The in vitro inhibitory activities on FAS of 22 extracts of spices were assessed by spectrophotometrically monitoring oxidation of NADPH at 340 nm. Results showed that 20 spices extracts (90.9 %) exhibited inhibitory activities on FAS, with half inhibition concentration (IC(50)) values ranging from 1.72 to 810.7 µg/ml. Among them, seven spices showed strong inhibitory effect with IC(50) values lower than 10 µg/ml. These findings suggest that a large proportion of the dietary spices studied possess promising inhibitory activities on FAS, and subsequently might be applied in the treatment of obesity and obesity-related human diseases.

Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells.

BACKGROUND: Fatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-cancer effect. In our previous study, alpha-mangostin had been found both fast-binding and slow-binding inhibitions to FAS in vitro. This study was designed to investigate the activity of alpha-mangostin on intracellular FAS activity in FAS over-expressed human breast cancer cells, and to testify whether the anti-cancer activity of alpha-mangostin may be related to its inhibitory effect on FAS. METHODS: We evaluated the cytotoxicity of alpha-mangostin in human breast cancer MCF-7 and MDA-MB-231 cells. Intracellular FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell viability. Immunoblot analysis was performed to detect FAS expression level, intracellular fatty acid accumulation and cell signaling (FAK, ERK1/2 and AKT). Apoptotic effects were detected by flow cytometry and immunoblot analysis of PARP, Bax and Bcl-2. Small interfering RNA was used to down-regulate FAS expression and/or activity. RESULTS: Alpha-mangostin could effectively suppress FAS expression and inhibit intracellular FAS activity, and result in decrease of intracellular fatty acid accumulation. It could also reduce cell viability, induce apoptosis in human breast cancer cells, increase in the levels of the PARP cleavage product, and attenuate the balance between anti-apoptotic and pro-apoptotic proteins of the Bcl-2 family. Moreover, alpha-mangostin inhibited the phosphorylation of FAK. However, the active forms of AKT, and ERK1/2 proteins were not involved in the changes of FAS expression induced by alpha-mangostin. CONCLUSIONS: Alpha-mangostin induced breast cancer cell apoptosis by inhibiting FAS, which provide a basis for the development of xanthone as an agent for breast cancer therapy.

Curcumin induces apoptosis of HepG2 cells via inhibiting fatty acid synthase.

Fatty acid synthase (FAS) is highly expressed in many kinds of human cancers, including liver cancer. Curcumin is the major active ingredient of Curcuma longa and has long been used to treat a variety of maladies. In the present study, we investigated the potential use of curcumin as a kind of FAS inhibitor for chemoprevention of liver cancer. Curcumin induced HepG2 cell apoptosis with the IC50 value of 8.84 µg/ml. It inhibited intracellular FAS activity, and downregulated expression and mRNA level of FAS in a dose-dependent manner. In addition, sodium palmitate could rescue cell apoptosis induced by curcumin. Further studies reviewed that siRNA of FAS showed similar results as curcumin. These findings suggested that curcumin might be useful for preventing or treating liver cancer.

Inhibitory effect of desoxyrhaponticin and rhaponticin, two natural stilbene glycosides from the Tibetan nutritional food Rheum tanguticum Maxim. ex Balf., on fatty acid synthase and human breast cancer cells.

Fatty acid synthase (FAS) has attracted more and more attention as a potential target for cancer treatment. Natural FAS inhibitors are emerging as potential therapeutic agents to treat cancer. Rheum tanguticum Maxim. ex Balf. (rhubarb) is a traditional Chinese nutritional food and has been reported to possess a variety of biological activities, including the ability to induce the apoptosis of cancer cells. This study indicates that desoxyrhaponticin (DC) and rhaponticin (RC), two stilbene glycosides from rhubarb, could be considered as promising FAS inhibitors. We found that both DC and RC could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells. In addition, the apoptotic effect of DC on human cancer cells was announced for the first time. Since FAS plays a key role in the biosynthesis pathway of fatty acids in cancer cells, these findings suggest that DC has potential applications in the prevention and treatment of cancer.

Inhibitory effects of grape skin extract and resveratrol on fatty acid synthase.

BACKGROUND: Grape skin, a rich source of phytochemicals, has been reported to possess remarkable anti-obesity activity. Fatty acid synthase (FAS) is a key enzyme catalyzing the synthesis of fatty acid de novo, and has been considered as an anti-obesity target. To elucidate the anti-obesity mechanism of grape skin, we investigated the effects of grape skin extract (GSE) and resveratrol, one of the phytochemicals in GSE, on FAS and FAS over-expressed 3 T3-L1 preadipocyte. METHODS: Purified FAS was obtained from chicken liver. Dried grape skin was extracted by 50% ethanol and partitioned by ethyl acetate. Inhibitory effects of GSE and resveratrol on FAS including fast-binding inhibition, time-dependent inhibition, and enzyme kinetics were determined. Inhibitory effects of GSE and resveratrol on 3T3-L1 preadipocyte were also measured. RESULTS: GSE inhibited the overall reaction and ß-ketoacyl reductase (KR) reaction of FAS with IC50 values of 4.61 µg/ml and 20.3 µg/ml. For inhibition by resveratrol, the relevant IC50 values were 11.1 µg/ml and 21.9 µg/ml, respectively. And both GSE and resveratrol showed time-dependent inhibition for FAS, with the kobs values of 0.028 min-1, and 0.040 min-1 respectively. They inhibited the overall reaction of FAS competitively with acetyl-CoA, noncompetitively with malonyl-CoA and in a mixed manner with NADPH. Moreover, the inhibition on KR domain by resveratrol was time-dependent with kobs value of 0.106 min-1. In 3 T3-L1 preadipocytes, resveratrol reduced lipid accumulation remarkably. CONCLUSIONS: GSE and resveratrol are potent FAS inhibitors and they bound reversibly to the KR domain of FAS to inhibit the reduction of the saturated acyl groups in fatty acid synthesis. Based on the valid data and deliberate analysis, we proposed that GSE and resveratrol have great medical potential and officinal value in treating obesity and related diseases.

Inhibitory effects of tannic acid on fatty acid synthase and 3T3-L1 preadipocyte.

Tannic acid is a hydrolyzable tannin that exists in many widespread edible plants with a variety of biological activities. In this study, we found that tannic acid potently inhibited the activity of fatty acid synthase (FAS) in a concentration-dependent manner with a half-inhibitory concentration value (IC50) of 0.14 microM. The inhibition kinetic results showed that the inhibition of FAS by tannic acid was mixed competitive and noncompetitive manner with respect to acetyl-CoA and malonyl-CoA, but uncompetitive to NADPH. Tannic acid prevented the differentiation of 3T3-L1 pre-adipocytes, and thus repressed intracellular lipid accumulation. In the meantime, tannic acid decreased the expression of FAS and down-regulated the mRNA level of FAS and PPARgamma during adipocyte differentiation. Further studies showed that the inhibitory effect of tannic acid did not relate to FAS non-specific sedimentation. Since FAS was believed to be a therapeutic target of obesity, these findings suggested that tannic acid was considered having potential in the prevention of obesity.

α-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase.

α-Mangostin, isolated from the hulls of Garcinia mangostana L., was found to have in vitro cytotoxicity against 3T3-L1 cells as well as inhibiting fatty acid synthase (FAS, EC 2.3.1.85). Our studies showed that the cytotoxicity of α-mangostin with IC(50) value of 20 µM was incomplicated in apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (ΔΨm) loss. This cytotoxicity was accompanied by the reduction of FAS activity in cells and could be rescued by 50 µM or 100 µM exogenous palmitic acids, which suggested that the apoptosis of 3T3-L1 preadipocytes induced by α-mangostin was via inhibition of FAS. Futhermore, α-mangostin could suppress intracellular lipid accumulation in the differentiating adipocytes and stimulated lipolysis in mature adipocytes, which was also related to its inhibition of FAS. In addition, 3T3-L1 preadipocytes were more susceptible to the cytotoxic effect of α-mangostin than mature adipocytes. Further studies showed that α-mangostin inhibited FAS probably by stronger action on the ketoacyl synthase domain and weaker action on the acetyl/malonyl transferase domain. These findings suggested that α-mangostin might be useful for preventing or treating obesity.

Inhibitory effects of onion (Allium cepa L.) extract on proliferation of cancer cells and adipocytes via inhibiting fatty acid synthase.

Onions (Allium cepa L.) are widely used in the food industry for its nutritional and aromatic properties. Our studies showed that ethyl acetate extract of onion (EEO) had potent inhibitory effects on animal fatty acid synthase (FAS), and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells. Furthermore, this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids, the final product of FAS catalyzed synthesis. These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS. We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes, which was also related to its inhibition of intracellular FAS activity. Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers, these findings suggested that onion might be useful for preventing obesity-related malignancy.

Fatty acid synthase inhibitors from the hulls of Nephelium lappaceum L.

Natural products inhibiting fatty acid synthase (FAS) are appearing as potential therapeutic agents to treat cancer and obesity. The bioassay-guided chemical investigation of the hulls of Nephelium lappaceum L. resulted in the isolation of ten compounds (1-10) mainly including flavonoids and oleane-type triterpene oligoglycosides, in which all of the compounds were isolated from this plant for the first time. Additionally, compounds 8 and 9 were new hederagenin derivatives and were elucidated as hederagenin 3-O-(2,3-di-O-acetyl-α-l-arabinofuranosyl)-(1→3)-[α-l-rhamnopyranosyl(1→2)]-ß-l-arabinopyranoside and hederagenin 3-O-(3-O-acetyl-α-l-arabinofuranosyl)-(1→3)-[α-l-rhamnopyranosyl-(1→2)]-ß-l-arabinopyranoside, respectively. All these isolates were evaluated for inhibitory activities of FAS, which showed these isolates had inhibitory activity against FAS with IC(50) values ranging from 6.69 to 204.40 µM, comparable to the known FAS inhibitor EGCG (IC(50)=51.97 µM). The study indicates that the hulls of Nephelium lappaceum L. could be considered as potential sources of promising FAS inhibitors and the oleane-type triterpene oligoglycosides could be considered as another type of natural FAS inhibitors.

Suppression of fatty acid synthase, differentiation and lipid accumulation in adipocytes by curcumin.

Curcumin is a well-known component of the cook seasoning and traditional herb turmeric (Curcuma longa), which has been reported to prevent obesity. However, the mechanism still remains to be determined. In this study, curcumin is found to be an effective inhibitor of fatty acid synthase (FAS), and its effects on adipocytes are further evaluated. Curcumin shows both fast-binding and slow-binding inhibitions to FAS. Curcumin inhibits FAS with an IC50 value of 26.8 µM, noncompetitively with respect to NADPH, and partially competitively against both substrates acetyl-CoA and malonyl-CoA. This suggests that the malonyl/acetyl transferase domain of FAS possibly is the main target of curcumin. The time-dependent inactivation shows that curcumin inactivates FAS with two-step irreversible inhibition, a specific reversible binding followed by an irreversible modification by curcumin. Like other classic FAS inhibitors, curcumin prevents the differentiation of 3T3-L1 cells, and thus represses lipid accumulation. In the meantime, curcumin decreases the expression of FAS, down-regulates the mRNA level of PPARγ and CD36 during adipocyte differentiation. Curcumin is reported here as a novel FAS inhibitor, and it suppresses adipocyte differentiation and lipid accumulation, which is associated with its inhibition of FAS. Hence, curcumin is considered to be having potential application in the prevention of obesity.

Substrate-induced changes in protease active site conformation impact on subsequent reactions with substrates.

Enzymatic catalysis of biochemical reactions is essential to all living systems. The "lock and key" and "induced fit" models were early contributions to our understanding of the mechanisms involved in the reaction between an enzyme and its substrate. However, whether a given substrate-induced conformation is rigid or remains flexible has not yet been determined. By measuring the enzyme activity and intrinsic fluorescence of a nonspecific Eisenia fetida protease-I with different chromogenic substrates, we show that in subsequent reactions of protease with substrates, both the "lock and key" and "induced fit" mechanisms are used depending on the degree of conformational change required. Chromozym-Th- or chromosym-Ch-induced protease conformations were unable to bind chromozym-U. The chromosym-U-induced protease conformation remained flexible and could be further induced by chromozym-Th and chromozym-Ch. When low concentrations of guanidine HCl were used to disturb the conformation of the enzyme, only small changes in intrinsic fluorescence of the chromozym-Th-induced protease were detected, in contrast to the native enzyme whose intrinsic fluorescence markedly increased. This indicates that the substrate-induced enzyme was relatively rigid compared with the native protease. Utilizing a lock and key mechanism for secondary substrate reactions may have adaptive value in that it facilitates high efficiency in enzymatic reactions.

Evaluation of inhibition of fatty acid synthase by ursolic acid: positive cooperation mechanism.

The inhibitory effect of ursolic acid (UA) on fatty acid synthase (FAS, EC 2.3.1.85) was investigated. We found that UA potently inhibited the activity of FAS with a half-inhibitory concentration value (IC(50)) of 6.0 microg/ml. The inhibition kinetic results showed that the inhibition of FAS by UA was competitive against acetyl-CoA and malonyl-CoA, but uncompetitive to NADPH. UA at low concentration slowly inactivated FAS, but FAS was fast inactivated by high concentration of UA in a positive cooperative manner. Moreover, NADPH significantly enhanced the inactivation of FAS by low concentration of UA, but NADPH slightly decreased the inactivation of FAS by high concentration of UA. Taken together, the results suggest that ursolic acid decreases the FAS activity through inactivation of acetyl/malonyl transferase. The combination of NADPH and KR domain promotes the inhibitory effect of UA on FAS.

Inhibitory effects of thioethers on fatty acid synthase and 3T3-L1 cells.

Thioethers are the main flavor compounds found in Liliaceae Allium vegetables and have been shown to have beneficial effects against several diseases correlated with metabolic syndrome. The inhibitory effects of six thioethers on fatty acid synthase (FAS) were investigated. Dose-dependent and time-dependent inhibitions of FAS by one trisulfide and two disulfides were revealed. Diallyl trisulfide (DATS, IC(50) = 8.37 microM) was the most active of these thioethers. Inhibition kinetics, substrate protection analysis, and stoichiometric assay revealed that DATS interacted with both essential sulfhydryl groups on the acyl-carrier protein and beta-ketoacyl synthase domain of FAS to inactivate the enzyme. The inactivation by DATS represented affinity-labeling kinetics. The active thioethers also inhibited the differentiation and lipid accumulation of 3T3-L1 preadipocytes, and the effect was related to their inhibition of FAS. It is suggested that the inhibition on FAS by thioethers and Allium vegetables is an important factor for their effects against metabolic syndrome.

Inhibitory effects on bacterial growth and beta-ketoacyl-ACP reductase by different species of maple leaf extracts and tannic acid.

It is important to develop new antibiotics aimed at novel targets. The investigation found that the leaf extracts from five maples (Acer platanoides, Acer campestre, Acer rubrum, Acer saccharum and Acer truncatum Bunge collected in Denmark, Canada and China) and their component tannic acid displayed antibacterial ability against 24 standard bacteria strains with the minimum inhibitory concentration of 0.3-8.0 mg/mL. Unlike the standard antibiotic levofloxacin (LFX), these samples inhibited Gram-positive bacteria more effectively than they inhibited Gram-negative bacteria. These samples effectively inhibited two antidrug bacterial strains. The results show that these samples inhibit bacteria by a different mechanism from LFX. These samples potently inhibited b-ketoacyl-ACP reductase (FabG), which is an important enzyme in bacterial fatty acid synthesis. Tannic acid showed the strongest inhibition on FabG with a half inhibition concentration of 0.78 microM (0.81 microg/mL). Furthermore, tannic acid and two maple leaf extracts showed time-dependent irreversible inhibition of FabG. These three samples also exhibited better inhibition on bacteria. It is suggested that FabG is the antibacteria target of maple leaf extracts and tannic acid, and both reversible and irreversible inhibitions of FabG are important for the antibacterial effect.

Novel and potent inhibitors of fatty acid synthase derived from catechins and their inhibition on MCF-7 cells.

Fatty acid synthase (FAS) is a potential target for cancer, but potent inhibitors against FAS are scarce. In this study, we found that activities of catechins on inhibiting FAS increased greatly by heating them in acid. The enhancement was positively correlated to H(+) concentration. The inhibitory activities of the final products from different catechins were similar, all of which were less than 1 microg/mL. The product from (-)-epigallocatechin gallate (EGCG) was stable at room temperature, and its inhibitory kinetics and reacting sites on FAS were obviously different from the known FAS inhibitors. It also affected the viability of MCF-7 cells more obviously than EGCG. A putative route of the reaction progress was proposed and the effective inhibitors were deduced to be oligomers of 2-hydroxy-3-(3', 4', 5'-trihydroxyphenyl) propenoic acid by analysis of their spectra. The work affords new and potent FAS inhibitors that would be promising candidates for the treatment of cancer.

Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions.

Black tea is recently reported to have anti-carcinogenic effects through pro-oxidant property, but the underlying mechanisms remain unclear. Mammalian cytosolic thioredoxin reductase (TrxR1) is well -known for its anti-oxidation activity. In this study, we found that black tea extract (BTE) and theaflavins (TFs), the major black tea polyphenols, inhibited the purified TrxR1 with IC(50) 44 microg/ml and 21+/-1 microg/ml, respectively. Kinetics of TFs exhibited a mixed type of competitive and non-competitive inhibition, with K(is) 4+/-1 microg/ml and K(ii) 26+/-5 microg/ml against coenzyme NADPH, and with K(is) 12+/-3 microg/ml and K(ii) 27+/-5 microg/ml against substrate DTNB. In addition, TFs inhibited TrxR1 in a time-dependent manner. In an equilibrium step, a reversible TrxR1-TFs complex (E*I) forms, which is followed by a slow irreversible first-order inactivation step. Rate constant of the inactivation was 0.7 min(-1), and dissociation constant of E*I was 51.9 microg/ml. Treatment of NADPH-reduced TrxR1 with TFs decreased 5-(Iodoacetamido) fluorescein incorporation, a fluorescent thiol-reactive reagent, suggesting that Sec/Cys residue(s) in the active site may be involved in the binding of TFs. The inhibitory capacity of TFs depends on their structure. Among the TFs tested, gallated forms had strong inhibitory effects. The interactions between TFs and TrxR1 were investigated by molecular docking, which revealed important features of the binding mechanism of theaflavins. An inhibitory effect of BTE on viability of HeLa cells was observed with IC(50) 29 microg/ml. At 33 microg/ml of BTE, TrxR1 activity in HeLa cells was decreased by 73% at 22 h after BTE treatment. TFs inhibited cell viability with IC(50) 10+/-4 microg/ml for HeLa cells and with IC(50) 20+/-5 microg/ml for EAhy926 cells. The cell susceptibility to TFs was inversely correlated to cellular levels of TrxR1. The inhibitory actions of TFs on TrxR1 may be an important mechanism of their anti-cancer properties.