RESUMEN
Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R-Ankrd1-P53 signaling pathway.
Asunto(s)
Medicamentos Herbarios Chinos , Infarto del Miocardio , Animales , Ratas , Apoptosis , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Fibrosis , Proteínas Musculares/efectos de los fármacos , Proteínas Musculares/metabolismo , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Nucleares/efectos de los fármacos , Proteínas Nucleares/metabolismo , Receptor de Angiotensina Tipo 1/efectos de los fármacos , Receptor de Angiotensina Tipo 1/metabolismo , Proteínas Represoras/efectos de los fármacos , Proteínas Represoras/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Increased activity of the lysine methyltransferase NSD2 driven by translocation and activating mutations is associated with multiple myeloma and acute lymphoblastic leukemia, but no NSD2-targeting chemical probe has been reported to date. Here, we present the first antagonists that block the protein-protein interaction between the N-terminal PWWP domain of NSD2 and H3K36me2. Using virtual screening and experimental validation, we identified the small-molecule antagonist 3f, which binds to the NSD2-PWWP1 domain with a Kd of 3.4 µM and abrogates histone H3K36me2 binding to the PWWP1 domain in cells. This study establishes an alternative approach to targeting NSD2 and provides a small-molecule antagonist that can be further optimized into a chemical probe to better understand the cellular function of this protein.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Proteínas Represoras/antagonistas & inhibidores , Simulación por Computador , Cristalografía por Rayos X , Descubrimiento de Drogas/métodos , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , N-Metiltransferasa de Histona-Lisina/efectos de los fármacos , Humanos , Ligandos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Dominios Proteicos , Proteínas Represoras/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas , Relación Estructura-ActividadRESUMEN
Flavaglines are cyclopenta[b]benzofurans found in plants of the genus Aglaia, several species of which are used in traditional Chinese medicine. These compounds target the initiation factor of translation eIF4A and the scaffold proteins prohibitins-1 and 2 (PHB1/2) to exert various pharmacological activities, including antiviral effects against several types of viruses, including coronaviruses. This review is focused on the antiviral effects of flavaglines and their therapeutic potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Asunto(s)
Aglaia/química , Antivirales/uso terapéutico , Productos Biológicos/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Factor 4A Eucariótico de Iniciación/genética , Neumonía Viral/tratamiento farmacológico , Proteínas Represoras/genética , Animales , COVID-19 , Factor 4A Eucariótico de Iniciación/efectos de los fármacos , Humanos , Medicina Tradicional China , Pandemias , Prohibitinas , Proteínas Represoras/efectos de los fármacosRESUMEN
The increasing incidence of antimicrobial-resistant bacterial pathogens has focused researchers on quorum sensing inhibition strategies instead of those conventional approaches to fight bacterial infections. Anti-quorum sensing (QS) activity of aqueous extract from Forsythia suspense (FSE) was assessed, and its potential QS inhibition mechanisms were also analyzed. The minimal inhibitory concentration (MIC) of FSE to Chromobacterium violaceum 12472 is 0.5 mg mL-1. Inhibition of QS-regulated violacein production and biofilm formation in C. violaceum 12472 by FSE occurred in a concentration-dependent manner at sub-MIC, with > 70.12 and > 85.31% inhibition at 0.25 mg mL-1, respectively. N-Acyl homoserine lactones (AHLs) extracted from cultures of C. violaceum 31532 grown in the presence of FSE could not change the violacein production in C. violaceum 026, which indicated that FSE did not inhibit AHL synthesis. We also found that FSE cannot degrade AHLs. Finally, in silico molecular docking was conducted. The computed binding energy data suggested that components of F. suspense have a tendency to inhibit CviR with varying binding affinities and the energy score of Pinoresinol (- 26.02 kcal/mol) is higher than that of C6-HSL (- 16.09 kcal mol-1). We concluded that FSE acts as an antagonist of bacterial quorum sensing by competing with AHL receptor binding site.
Asunto(s)
Chromobacterium/efectos de los fármacos , Forsythia , Extractos Vegetales/farmacología , Percepción de Quorum/efectos de los fármacos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Indoles/metabolismo , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular/métodos , Extractos Vegetales/química , Proteínas Represoras/efectos de los fármacos , Proteínas Represoras/metabolismo , Transactivadores/efectos de los fármacos , Transactivadores/metabolismoRESUMEN
Dysregulated human monocytes/macrophages can synthesize and secrete matrix metalloproteinases (MMPs), which play important roles in the progression of sepsis. In this study, we investigated the effects and mechanism of a novel histone deacetylase (HDAC8) inhibitor, (E)-N-hydroxy-4-methoxy-2-(biphenyl-4-yl)cinnamide (WK2-16), on MMP-9 production and activation in stimulated human monocytic THP-1 cells. Our results demonstrated that the acetylation level of structural maintenance of chromosomes 3 (SMC3) was up-regulated by WK2-16 in THP-1 cells. Consistently, an in vitro enzyme study demonstrated that WK2-16 selectively inhibited HDAC8 activity. Moreover, the WK2-16 concentration dependently suppressed MMP-9-mediated gelatinolysis induced by tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS). Additionally, WK2-16 significantly inhibited both MMP-9 protein and mRNA expression without cellular toxicity. Nevertheless, WK2-16 suppressed the extracellular levels of interleukin (IL)-6 from LPS-stimulated THP-1 cells. For the signaling studies, WK2-16 had no effect on LPS/TLR4 downstream signaling pathways, such as the NF-κB and ERK/JNK/P38 MAPK pathways. On the other hand, WK2-16 enhanced the recruitment of acetylated Yin Yang 1 (YY1) with HDAC1. Finally, in vivo studies indicated that WK2-16 could reduce the serum levels of TNF-α and IL-6 in endotoxemic mice. These results suggested that HDAC8 inhibition might provide a novel therapeutic strategy of hypercytokinemia in sepsis.
Asunto(s)
Citocinas/efectos de los fármacos , Citocinas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/efectos de los fármacos , Histona Desacetilasas/metabolismo , Lipopolisacáridos/farmacología , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Represoras/efectos de los fármacos , Proteínas Represoras/metabolismo , Acetilación , Animales , Proteínas de Ciclo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Ciclooxigenasa 2/efectos de los fármacos , Regulación hacia Abajo , Endotoxemia , Histona Desacetilasa 1/efectos de los fármacos , Humanos , Interleucina-6 , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/metabolismo , FN-kappa B/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/efectos de los fármacos , Sepsis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Células THP-1/efectos de los fármacos , Tubulina (Proteína)/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Factor de Transcripción YY1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacosRESUMEN
BACKGROUND: The scope of this work was to study synergism between human papillomavirus (HPV) infection and tobacco in vitro, both known to be independent risk factors for oral cancer. METHODS: HPV-positive and HPV-negative oral keratinocytes and oral HPV-negative fibroblasts were exposed to smokeless tobacco extract (STE) prepared from the Scandinavian (STE1) and US-type (STE2) snuff. Cell cycle profiles were determined with flow cytometry, and HPV E6/E7 mRNA expression in HPV-positive cells was assayed using RT-qPCR. RESULTS: The exposure of HPV-positive keratinocytes with STE2 increased the number of aneuploid cells from 27% to 80% of which 44% were in S-phase, while none of the diploid cells were in S-phase. The changes after STE1 exposure were less than seen after STE2: from 27% to 31% of which 34% were in S-phase. STE had no effect on HPV16 E6/E7 expression in HPV-positive keratinocytes. In oral spontaneously transformed, HPV-negative keratinocytes, the number of aneuploid cells at G2-M stage increased after STE1 and STE2 exposure from 3% to 9% and 7%, respectively. In HPV-negative oral fibroblasts, the number of cells at G2-M phase increased from 11% to 21% after STE1 and 29% after STE2 exposure. CONCLUSIONS: The effect of STE varied in the cell lines studied. STE2 increased significantly the proportion of aneuploid cells in HPV-positive oral keratinocytes, but not HPV16 E6/E7 expression. This indicates that tobacco products may enhance the effects of HPV 16 and the risk of DNA aneuploidy increasing risk to malignant transformation.
Asunto(s)
Aneugénicos/efectos adversos , Aneuploidia , Transformación Celular Viral/fisiología , Papillomavirus Humano 16/fisiología , Queratinocitos/efectos de los fármacos , Mucosa Bucal/efectos de los fármacos , Extractos Vegetales/efectos adversos , Tabaco sin Humo/efectos adversos , División Celular/efectos de los fármacos , Línea Celular , Línea Celular Transformada , Diploidia , Fibroblastos/efectos de los fármacos , Fibroblastos/virología , Fase G2/efectos de los fármacos , Encía/citología , Encía/virología , Humanos , Queratinocitos/virología , Mucosa Bucal/citología , Mucosa Bucal/virología , Nicotina/efectos adversos , Proteínas Oncogénicas Virales/análisis , Proteínas Oncogénicas Virales/efectos de los fármacos , Proteínas E7 de Papillomavirus/análisis , Proteínas E7 de Papillomavirus/efectos de los fármacos , Proteínas Represoras/análisis , Proteínas Represoras/efectos de los fármacos , Fase S/efectos de los fármacos , Piel/citología , Piel/virología , TetraploidíaRESUMEN
Quorum sensing (QS) is a process by which bacteria use small molecules or peptidic signals to assess their local population densities. At sufficiently high density, bacteria can alter gene expression levels to regulate group behaviors involved in a range of important and diverse phenotypes, including virulence factor production, biofilm formation, root nodulation, and bioluminescence. Gram-negative bacteria most commonly use N-acylated l-homoserine lactones (AHLs) as their QS signals. The AHL lactone ring is hydrolyzed relatively rapidly at biological pH, and the ring-opened product is QS inactive. We seek to identify AHL analogues with heightened hydrolytic stability, and thereby potentially heightened activity, for use as non-native modulators of bacterial QS. As part of this effort, we probed the utility of thiolactone analogues in the current study as QS agonists and antagonists in Gram-negative bacteria. A focused library of thiolactone analogs was designed and rapidly synthesized in solution. We examined the activity of the library as agonists and antagonists of LuxR-type QS receptors in Pseudomonas aeruginosa (LasR), Vibrio fischeri (LuxR), and Agrobacterium tumefaciens (TraR) using bacterial reporter strains. The thiolactone library contained several highly active compounds, including some of the most active LuxR inhibitors and the most active synthetic TraR agonist reported to date. Analysis of a representative thiolactone analog revealed that its hydrolysis half-life was almost double that of its parent AHL in bacterial growth medium.
Asunto(s)
Acil-Butirolactonas/síntesis química , Bacterias Gramnegativas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Proteínas Represoras/efectos de los fármacos , Transactivadores/efectos de los fármacos , Acetilación , Acil-Butirolactonas/química , Acil-Butirolactonas/farmacocinética , Acil-Butirolactonas/farmacología , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Genes Reporteros/efectos de los fármacos , Bacterias Gramnegativas/genética , Bacterias Gramnegativas/metabolismo , Hidrólisis , Terapia Molecular Dirigida , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Percepción de Quorum/fisiología , Proteínas Represoras/agonistas , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/fisiología , Transactivadores/agonistas , Transactivadores/antagonistas & inhibidores , Transactivadores/fisiologíaRESUMEN
Quorum sensing (QS) is a cell-cell signaling mechanism that allows bacteria to monitor their population size and alter their behavior at high cell densities. Gram-negative bacteria use N-acylated L-homoserine lactones (AHLs) as their primary signals for QS. These signals are susceptible to lactone hydrolysis in biologically relevant media, and the ring-opened products are inactive QS signals. We have previously identified a range of non-native AHLs capable of strongly agonizing and antagonizing QS in Gram-negative bacteria. However, these abiotic AHLs are also prone to hydrolysis and inactivation and thereby have a relatively short time window for use (â¼12-48 h). Non-native QS modulators with reduced or no hydrolytic instability could have enhanced potencies and would be valuable as tools to study the mechanisms of QS in a range of environments (for example, on eukaryotic hosts). This study reports the design and synthesis of two libraries of new, non-hydrolyzable AHL mimics. The libraries were screened for QS modulatory activity using LasR, LuxR, and TraR bacterial reporter strains, and several new, abiotic agonists and antagonists of these receptors were identified.
Asunto(s)
Acil-Butirolactonas/metabolismo , Diseño de Fármacos , Bacterias Gramnegativas/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Proteínas Represoras/efectos de los fármacos , Transactivadores/efectos de los fármacos , Acil-Butirolactonas/síntesis química , Acil-Butirolactonas/química , Acil-Butirolactonas/farmacología , Proteínas Bacterianas/agonistas , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/efectos de los fármacos , Proteínas Bacterianas/genética , Evaluación Preclínica de Medicamentos , Estabilidad de Medicamentos , Genes Reporteros/efectos de los fármacos , Bacterias Gramnegativas/fisiología , Lactonas/metabolismo , Terapia Molecular Dirigida , Proteínas Represoras/agonistas , Proteínas Represoras/genética , Proteínas Represoras/fisiología , Transactivadores/agonistas , Transactivadores/antagonistas & inhibidores , Transactivadores/genética , Transactivadores/fisiologíaAsunto(s)
Catequina/análogos & derivados , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Neoplasias Cutáneas/genética , Animales , Anticarcinógenos , Catequina/farmacología , Dieta , Epidermis/química , Epigénesis Genética , Humanos , Ratones , Proteínas Nucleares/efectos de los fármacos , Proteínas Nucleares/fisiología , Complejo Represivo Polycomb 1 , Proteínas Proto-Oncogénicas/efectos de los fármacos , Proteínas Proto-Oncogénicas/fisiología , Proteínas Represoras/efectos de los fármacos , Proteínas Represoras/fisiología , Neoplasias Cutáneas/prevención & control , Té/químicaRESUMEN
Jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone) was isolated from Artemisia argyi as a putative oncogene inhibitor. Jaceosidin inhibited binding between oncoprotein E6 of the human papillomavirus and the p53 tumor suppressor protein. In addition, jaceosidin inhibited binding between the E7 oncoprotein and the Rb tumor suppressor protein, and also inhibited the function of HPV-16 harboring cervical cancer cells, including SiHa and CaSki. Collectively, jaceosidin inhibited the functions of the E6 and E7 oncoproteins of the human papillomavirus, suggesting that this compound might be used as a potential drug for the treatment of cervical cancers associated with the human papillomavirus.
Asunto(s)
Artemisia , Flavonoides/farmacología , Proteínas Oncogénicas Virales/efectos de los fármacos , Proteínas Represoras/efectos de los fármacos , Células Tumorales Cultivadas/efectos de los fármacos , Neoplasias del Cuello Uterino , Supervivencia Celular/efectos de los fármacos , Femenino , Flavonoides/aislamiento & purificación , Humanos , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus , Hojas de la Planta , Proteínas Represoras/metabolismoRESUMEN
The development of skeletal muscle in mammals is promoted by the muscle-specific basic helix-loop-helix transcription factors of the MyoD family. Evidence also suggests that there are basic helix-loop-helix proteins that specifically inhibit skeletal myogenesis, including Mtwist, Mist1, and the most recently described, MyoR. It has been suggested that MyoR expression is limited to the precursors of the skeletal muscle lineage and acts as a transcriptional repressor of the muscle differentiation program. However, our results demonstrate that MyoR is expressed in several different, nonmuscle adult tissues. Furthermore, MyoR is expressed in the embryonic ectoderm of blastocyst stage mouse embryos, well before skeletal muscle specification and even before delineation of the mesodermal germ layer. Using embryonic ectoderm analogous stem cells, we demonstrate that in these nonmuscle cells, as in skeletal muscle precursor cells, expression of MyoR is inversely correlated with the extent of cellular differentiation as induced by retinoic acid. Our preliminary results indicate that overexpression of exogenous MyoR inhibits retinoic-acid-induced differentiation in EC cells and is lethal to early mouse embryos. Our results suggest a much broader role for MyoR in the repression and/or determination of embryonic cell differentiation.
Asunto(s)
Diferenciación Celular/fisiología , Ectodermo/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Ratones/embriología , Células Madre/metabolismo , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Linaje de la Célula/efectos de los fármacos , Linaje de la Célula/fisiología , ADN Complementario/análisis , ADN Complementario/genética , Ectodermo/citología , Feto , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Genes Letales/efectos de los fármacos , Genes Letales/genética , Genes Reguladores/efectos de los fármacos , Genes Reguladores/fisiología , Ratones/metabolismo , Ratones Transgénicos/genética , Ratones Transgénicos/metabolismo , Datos de Secuencia Molecular , Proteínas Musculares , Proteínas Represoras/efectos de los fármacos , Proteínas Represoras/metabolismo , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie , Células Madre/citología , Factores de Transcripción/genética , Factores de Transcripción/aislamiento & purificación , Tretinoina/farmacologíaRESUMEN
Ayurveda, the ancient Indian system of health care and medicine, has a well-organized materia medica in which plants form a dominant part. A key illustration of the exploitation of this knowledge toward the development of a modern drug is the isolation and characterization of two antihyperlipidemic compounds, Z-, and E-guggulsterone from the tree Commiphora mukul, the exudate of which has been traditionally used for mitigating lipid disorders. Here, we demonstrate that Z-guggulsterone and an analog, 80-574 currently in clinical trials, act as antagonists of the bile acid receptor (BAR), a member of the intracellular receptor superfamily. These compounds antagonize the activity of BAR in vitro, and in cell culture systems on promoters and endogenous target genes. In biochemical assays, they are able to displace coactivator peptides from the receptor in a dose-dependent manner. The mechanism by which they act as BAR antagonists is likely through their inability to recruit coactivator proteins, failure to release corepressor proteins from unliganded receptor, and ability to compete with BAR agonists to block coactivator recruitment. Our data suggest these compounds may mediate at least some of their effects via the BAR.
Asunto(s)
Proteínas de Unión al ADN/antagonistas & inhibidores , Hidroxiesteroide Deshidrogenasas , Hipolipemiantes/farmacología , Glicoproteínas de Membrana , Pregnenodionas/farmacología , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Células Cultivadas , Colesterol 7-alfa-Hidroxilasa/efectos de los fármacos , Colesterol 7-alfa-Hidroxilasa/genética , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Isoxazoles/farmacología , Ligandos , Hígado/efectos de los fármacos , Hígado/metabolismo , Subunidad 1 del Complejo Mediador , Proteínas Nucleares/efectos de los fármacos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Co-Represor 1 de Receptor Nuclear , Pregnadienos/farmacología , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Hormona Tiroidea/efectos de los fármacos , Receptores de Hormona Tiroidea/metabolismo , Proteínas Represoras/efectos de los fármacos , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Transcripción/efectos de los fármacos , Factores de Transcripción/metabolismoRESUMEN
Tea catechins exert many biological effects, including anticancer and antibacterial activities. Also, it is reported that some plant flavonoids exhibit estrogenic activity. In this study, we investigated estrogenic or antiestrogenic activities of catechins in HeLa cells transiently transfected with an estrogen response element (ERE)-regulated luciferase reporter and an estrogen receptor (ER) alpha or ERbeta expression vector. Catechins alone did not induce luciferase (luc) activity in either of the ERs. Addition of 17beta-estradiol (E2) plus epicatechin gallate (ECG) or epigallocatechin gallate (EGCG) at 5 x 10(-6) M resulted in significant decreases in the ERalpha-mediated luc activity compared with that of E2 alone. On the contrary, lower concentrations significantly increased the E2-induced luc activity. Similar effects were observed with tamoxifen. The ERbeta-mediated estrogenic activities were stimulated by catechins. In conclusion, some catechins, particularly EGCG, were antiestrogenic for ERalpha at higher doses, and co-estrogenic for ERalpha at lower doses and for ERbeta. The lower doses were found in human plasma after tea-drinking. In addition, some catechins may be antiendocrine disruptors because they suppressed bisphenol A-induced luc activities.