Preventive Activity of Patchouli Alcohol Against Colorectal Cancer and Diabetes.

Patchouli alcohol (PA) is a tricyclic sesquiterpene and the dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). It has been reported to possess diverse health-beneficial activities, including anti-inflammatory, antiobese, and anticancer activities. However, preclinical studies are required to explore the possibility of developing PA as a promising functional and promising drug for the prevention and treatment of human diseases. In this study, we used animal models to examine whether PA shows benefits in inflammation-induced colorectal cancer and obesity-induced diabetes. ApcMin/+ mice for colorectal cancer model were treated PA 0, 25 and 50 mg/kg body weight three times a week for 6 weeks along with 2% dextran sulfate sodium (DSS) in drinking water for 1 week. High-fat diet (HFD)-induced obesity mice were treated with PA 0, 25, and 50 mg/kg bodyweight three times a week for 8 weeks. Oral administration of PA to ApcMin/+ mice treated with DSS significantly suppressed formation and development of tumors in both small and large intestines. In cell culture using Caco-2 human colorectal cancer cells, treatment of culture media with PA suppressed proliferation and induced G1-phase growth arrest. In a mouse model of HFD-induced obesity, glucose tolerance tests indicated the same orally administered dose of PA to significantly reduce blood glucose. In vitro assays in differentiated C2C12 myocytes further demonstrated PA to significantly enhance glucose uptake and increase phosphorylation of 5' adenosine monophosphate-activated protein kinase and protein kinase B. This study demonstrates that PA might possess health beneficial effects on colorectal cancer and obesity-induced diabetes.

Synthetic colourants in capsule dietary supplements on the Korean market.

This study developed a rapid and easy analytical method for the simultaneous determination of nine synthetic colourants (SCs) in capsule dietary supplements. Sample pretreatment involved thermal treatment to dissolve gelatin, using the enzymes protease and amylase to prevent the gelation of gelatin and fat-soluble substances removal using petroleum ether. The method was linear (r2 ≥0.999), with LOD of 0.009-0.029 µg/mL and LOQ of 0.42-1.40 µg/g. Recovery ranged from 90.9 to 108.9%. The relative expanded measurement uncertainty ranged from 4.1 to 6.3%. Allura Red AC (R40) and Brilliant Blue FCF (B1) were commonly detected in 20 of the 28 samples. Up to six SCs such as Tartrazine (Y4), Sunset yellow (Y5), Amaranth (R2), Erythrosine B (R3), R40 and B1 were detected in a single sample, ranging from 30.5 to 40.2 µg/g. Total content of SCs in various capsule supplements ranged from 0.3 to 73.7 µg/g.

Soluble Free, Soluble Conjugated, and Insoluble Bound Phenolics in Tomato Seeds and Their Radical Scavenging and Antiproliferative Activities.

The soluble free, soluble conjugated, and insoluble bound phenolic compounds in tomato seeds were extracted and analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Total phenolic content (TPC) and free radical scavenging activities along with the antiproliferative effects against the human colorectal cancer cell line (HCT-116) were also examined for the soluble free, soluble conjugated, and insoluble bound phenolic fractions. 13, 7, and 10 compounds were tentatively identified in the soluble free, soluble conjugated, and insoluble bound phenolic fractions, respectively, including indole-3-acetic acid derivatives, flavonoids, phenolic acid, and tyramine-derived hydroxycinnamic acid amines. The insoluble bound phenolic fraction was observed to have a greater TPC value and stronger free radical scavenging activities against ABTS•+, DPPH•, and peroxyl radicals and a stronger inhibitory effect against HCT-116 cells compared with the soluble free and the soluble conjugated fractions. Soluble free and insoluble bound fractions significantly inhibited the proliferation of the HCT-116 cell line, and no antiproliferative effects were observed with the soluble conjugated fraction under the experimental conditions. The results may provide a foundation for future application of tomato seeds as nutraceuticals in dietary supplements and functional foods.

Anti-Adipogenic Activity of High-Phenolic Sorghum Brans in Pre-Adipocytes.

Obesity is one of the leading public health problems that can result in life-threatening metabolic and chronic diseases such as cardiovascular diseases, diabetes, and cancer. Sorghum (Sorghum bicolor (L.) Moench) is the fifth most important cereal crop in the world and certain genotypes of sorghum have high polyphenol content. PI570481, SC84, and commercially available sumac sorghum are high-polyphenol genotypes that have demonstrated strong anti-cancer activities in previous studies. The objective of this study was to explore a potential anti-obesity use of extracts from sorghum bran in the differentiation of 3T3-L1 preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. None of the four different sorghum bran extracts (PI570481, SC84, Sumac, and white sorghum as a low-polyphenol control) caused cytotoxicity in undifferentiated and differentiated 3T3-L1 cells at doses used in this study. Sorghum bran extracts (PI570481, SC84, and Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in a dose-dependent manner in differentiated 3T3-L1 cells. The same polyphenol containing sorghum bran extracts also repressed production of reactive oxygen species (ROS) and MAPK signaling pathways and repressed insulin signaling and glucose uptake in differentiated 3T3-L1 cells. These data propose a potential use of high-phenolic sorghum bran for the prevention of obesity.

Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate.

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

Dietary probiotic and metabolites improve intestinal homeostasis and prevent colorectal cancer.

The excessive secretion of pro-inflammatory cytokines, uncontrolled cell proliferation, and dysbiosis in gut intestinal microbiota are involved in tumorigenesis and progression of colorectal cancer. Probiotics secrete various functional metabolites that maintain intestinal microflora balance and improve the host's gut health. This study defines the roles of dietary Lactobacillus (LC-CLA) metabolites, especially conjugated linoleic acids (CLA), in intestinal homeostasis. Based on cellular and transcriptional examination, LC-CLA cell free cultural supernatant (CFCS) significantly inhibited the viability of colorectal cancer cells (HCT-116). CFCSs containing various levels of CLA also significantly lowered the transcript levels of crucial genes for tumorous cell growth and proliferation, such as CDK1/2/6, PLK1, and SKP2. Furthermore, LC-CLA and its CFCS exhibited substantial free radical scavenging activities as well as downregulated pro-inflammatory cytokine and upregulated anti-inflammatory cytokine gene expressions. In addition, daily consumption of LC-CLA for one week modulated the composition of gut microflora by specifically reducing the relative abundance of sulfidogenic bacteria in mice. These findings reveal the potential application of CLA from probiotic origin as a dietary supplement or nutraceutical agent for improving gastrointestinal health and preventing colorectal cancer.

Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells.

Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.

Patchouli Alcohol, a Compound from Pogostemon cablin, Inhibits Obesity.

Obesity predisposes people to a variety of chronic metabolic diseases. Identification of natural factors that prevent the development of obesity is likely to be the most successful means of ameliorating the current obesity epidemic. Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin and possesses health benefit activities. This study was designed to examine if patchouli alcohol affects adipogenesis, and investigates the underlying mechanisms whereby patchouli alcohol exerts antiobesity effect. 3T3-L1 adipocytes were differentiated with treatment of different concentrations of patchouli alcohol. An in vivo study was performed to test the effect of patchouli alcohol gavage on a high-fat diet (HFD)-induced obesity. Treatment of patchouli alcohol reduced lipid accumulation in 3T3-L1 adipocytes in a dose-dependent manner without toxicity. Regarding mechanism, treatment of patchouli alcohol reduced expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT-enhancer-binding protein-alpha (C/EBPα) and increased expression of total and active ß-catenin in 3T3-L1 adipocytes. Oral gavage of patchouli alcohol led to a significant reduction of body weight and fat accumulation in the mice fed with HFD. Transcriptome analysis indicates that smad7 is most highly activated gene in patchouli alcohol-treated 3T3-L1 cells. Patchouli alcohol possesses health benefit effect through inhibiting adipogenesis and fat tissue development.

Development, physicochemical characterization and cytotoxicity of selenium nanoparticles stabilized by beta-lactoglobulin.

Novel Selenium nanoparticles (SeNPs) were developed using beta-lactoglobulin (Blg) as a stabilizer in redox systems of selenite and ascorbic acid in this study. Particle size, morphology, stability, and in vitro biological activity of synthesized Blg stabilized selenium nanoparticles (Blg-SeNPs) were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet-visible spectrophotometry (UV/Vis), and cell toxicity assays, respectively. Stabilizing mechanisms of Blg-SeNPs were investigated by Fourier-transform infrared spectroscopy (FTIR) and protein fluorescence probe. The results revealed that the Blg-SeNPs were spherical with mean particle size of 36.8±4.1nm. They were stable in acidic or neutral to basic solutions (pH 2.5-3.5 or 6.5-8.5) at 4°C for 30days as a result of electrostatic repulsions. FTIR results showed that functional groups of NH2 and OH on Blg molecules were responsible for binding with SeNPs. Furthermore, decreases in protein surface hydrophobicity indicated that possible binding happened between Se and the hydrophobic domains of Blg. The cell toxicity of Blg-SeNPs was significantly lower than that of sodium selenite on both cancerous and non-cancerous cells. This study provides a facile and green method for chemically synthesizing stable SeNPs which are suitable for further evaluation in medicinal applications.

3,3'-Diindolylmethane Suppresses Adipogenesis Using AMPKα-Dependent Mechanism in 3T3-L1 Adipocytes and Caenorhabditis elegans.

3,3'-diindolylmethane is a major in vivo metabolite of indole-3-carbinol, a bioactive compound found in cruciferous vegetables. Although 3,3'-diindolylmethane has been implicated to possess antitumorigenic and anti-inflammatory properties, the effect of 3,3'-diindolylmethane on adipogenesis has not been explored previously. Thus, the present study was conducted to determine if 3,3'-diindolylmethane affects adipogenesis using 3T3-L1 adipocytes and Caenorhabditis elegans. Treatment of 3,3'-diindolylmethane significantly reduced fat accumulation without affecting viability in 3T3-L1 adipocytes. 3,3'-diindolylmethane suppressed expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), fatty acid binding protein 4 (FABP4), and perilipin. In addition, 3,3'-diindolylmethane activated AMP-activated protein kinase α (AMPKα), which subsequently inactivated acetyl CoA carboxylase (ACC), resulting in reduced fat accumulation. These observations were further confirmed in C. elegans as treatment with 3,3'-diindolylmethane significantly reduced body fat accumulation, which was partly associated with aak-1, but not aak-2, orthologs of AMPKα catalytic subunits α1 and α2, respectively. The current results demonstrate that 3,3'-diindolylmethane, a biologically active metabolite of indole-3-carbinol, may prevent adipogenesis through the AMPKα-dependent pathway.

ß-Catenin Mediates Anti-adipogenic and Anticancer Effects of Arctigenin in Preadipocytes and Breast Cancer Cells.

Arctigenin is a lignan abundant in Asteraceae plants and has anti-inflammatory, antiobesity, and anticancer activities. Obesity is one of the leading causes of several types of cancers including breast cancer. The current study was performed to investigate if arctigenin suppresses differentiation of preadipocytes and proliferation of breast cancer cells and to explore potential molecular mechanisms. Treatment of arctigenin reduced lipid accumulation in differentiated 3T3-L1 adipocytes in a dose- and time-dependent manner without toxicity. Arctigenin suppressed the expression of peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein-alpha (C/EBPα), perilipin, and fatty acid binding protein 4 (FABP4) in a dose-dependent manner in differentiated 3T3-L1 cells. Both total and unphosphorylated (active) ß-catenin were increased in whole cell lysates and the nuclear fraction of differentiated 3T3-L1 cells treated with 25 µM arctigenin. On the other hand, arctigenin decreased proliferation of two human breast cancer cells (MCF-7 and MDA-MB-231). Arctigenin induced apoptosis and decreased expression of total and unphosphorylated (active) ß-catenin and cyclin D1 in MCF-7, but not in MDA-MB-231. These data indicate that arctigenin suppressed adipogenesis in preadipocytes and activated apoptosis in estrogen receptor (ER) positive breast cancer cells through modulating expression of ß-catenin.

Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of ß-catenin.

BACKGROUND AND PURPOSE: Aberrant expression of ß-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of ß-catenin. METHODS: In vitro effects of EGCG on the transcription, translation, or degradation of ß-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and ß-catenin expression was checked in HNC patients' samples. RESULTS: ß-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of ß-catenin signaling. Knockdown of ß-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of ß-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of ß-catenin. The suppression of ß-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits ß-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation. CONCLUSION: This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs.

Anticancer Properties of Capsaicin Against Human Cancer.

There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities.

Anti-inflammatory activity of mushroom-derived hispidin through blocking of NF-κB activation.

BACKGROUND: Hispidin, a polyphenol compound mainly derived from the valuable medicinal mushroom Phellinus species, has been found to possess distinct biological effects. However, the anti-inflammatory potential of hispidin still remains uncharacterized. RESULTS: In this study, the effects of hispidin on activation of nuclear factor kappa B (NF-κB) and the subsequent production of inducible nitric oxide synthase (iNOS) were determined in the lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cells. Our data indicated that hispidin inhibits transcriptional activity of NF-κB in a dose-dependent manner. Hispidin also attenuated LPS-induced NF-κB nuclear translocation and associated inhibitor of kappa B (IκB-α) degradation. Furthermore, hispidin deceased iNOS protein expression and the generation of reactive oxygen species (ROS) in the LPS-induced cells, but did not affect phosphorylation of mitogen-activated protein kinases. CONCLUSION: These findings suggest that hispidin exhibits anti-inflammatory activity through suppressing ROS mediated NF-κB pathway in mouse macrophage cells.

Anticancer activity of protocatechualdehyde in human breast cancer cells.

Protocatechualdehyde (PCA) is a natural polyphenol compound isolated from the root of the herb S. miltiorrhiza and barley tea plants. PCA possesses antiproliferative and pro-apoptotic properties in human colorectal cancer cells. However, the cellular mechanism has not been fully understood. ß-catenin and cyclin D1 are proto-oncogene that is overexpressed in many types of cancers and leads to cancer development. The present study was performed to elucidate the molecular mechanism by which PCA stimulates cell growth arrest and apoptosis in human breast cancer cells. PCA repressed cell proliferation and induced apoptosis in dose-dependent manner. PCA suppressed the expression of ß-catenin and cyclin D1 with no changes in mRNA levels. Inhibition of proteosomal degradation using MG-132 and Ada-(Ahx)3-(Leu)3-vinyl sulfone ameliorates PCA-induced downregulation of ß-catenin and cyclin D1. PCA treatment decreased the half-life of ß-catenin and cyclin D1. PCA-mediated ß-catenin downregulation depends on GSK3ß. We further provide the evidence that PCA increased nuclear translocation of nuclear factor kappa-B (NF-κB) and the blockage of NF-κB using Bay11-7082 inhibited PCA-mediated ß-catenin downregulation. The current study demonstrates that PCA suppress ß-catenin expression through GSK3ß- and NF-κB-mediated proteosomal degradation. In addition, PCA decreased cyclin D1 expression independent to ß-catenin through proteosomal degradation.

Capsaicin represses transcriptional activity of ß-catenin in human colorectal cancer cells.

Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters ß-catenin-dependent signaling in human colorectal cancer cells in vitro. Exposure of SW480, LoVo and HCT-116 cells to capsaicin suppressed cell proliferation. Transient transfection with a ß-catenin/T-cell factor (TCF)-responsive reporter indicated that capsaicin suppressed the transcriptional activity of ß-catenin/TCF. Capsaicin treatment resulted in a decrease of intracellular ß-catenin levels and a reduction of transcripts from the ß-catenin gene (CTNNB1). These results were confirmed by a reduced luciferase reporter activity driven by promoter-reporter construct containing the promoter region of the Catnb gene. In addition, capsaicin destabilized ß-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and ß-catenin. This study identifies a role for the ß-catenin/TCF-dependent pathway that potentially contributes to the anticancer activity of capsaicin in human colorectal cancer cells.

Antidiabetic Activities of Abutilon indicum (L.) Sweet Are Mediated by Enhancement of Adipocyte Differentiation and Activation of the GLUT1 Promoter.

Abutilon indicum (L.) Sweet is an Asian phytomedicine traditionally used to treat several disorders, including diabetes mellitus. However, molecular mechanisms supporting the antidiabetic effect of A. indicum L. remain unknown. The aim of this study was to evaluate whether extract of A. indicum L. improves insulin sensitivity. First, we observed the antidiabetic activity of aqueous extract of the entire plant (leaves, twigs and roots) of A. indicum L. on postprandial plasma glucose in diabetic rats. The subsequent experiments revealed that butanol fractions of the extract bind to PPARγ and activate 3T3-L1 differentiation. To measure glucose uptake enhanced by insulin-like activity, we used rat diaphragm incubated with various concentrations of the crude extract and found that the extract enhances glucose consumption in the incubated solution. Our data also indicate that the crude extract and the fractions (water and butanol) did not affect the activity of kinases involved in Akt and GSK-3ß pathways; however, the reporter assay showed that the crude extract could activate glucose transporter 1 (GLUT1) promoter activity. These results suggest that the extract from A. indicum L. may be beneficial for reducing insulin resistance through its potency in regulating adipocyte differentiation through PPARγ agonist activity, and increasing glucose utilization via GLUT1.

A green tea component suppresses posttranslational expression of basic fibroblast growth factor in colorectal cancer.

BACKGROUND & AIMS: Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis. However, the exact molecular mechanism by which EGCG suppresses bFGF expression is not known. Our objective was to elucidate the molecular mechanisms by which EGCG inhibits bFGF expression in colorectal cancer. METHODS: We examined posttranslational regulation of bFGF by EGCG in human colorectal cancer cells. We also examined bFGF in intestinal tumor formation of APC(Min/+) mice with and without catechin treatment. RESULTS: The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein. Furthermore, EGCG suppressed tumor formation in APC(Min/+) mice, compared with vehicle-treated mice, in association with reduced bFGF expression. CONCLUSIONS: The ubiquitin-proteasome degradation pathway contributes significantly to down-regulation of bFGF expression by EGCG. Catechin compounds have fewer adverse effects than chemotherapeutic agents and hence can be used as proof-of-concept in cancer therapeutics to suppress growth and metastasis by targeting proteins such as bFGF.

Green tea catechin (-)-epicatechin gallate induces tumour suppressor protein ATF3 via EGR-1 activation.

Epicatechin gallate (ECG) is the third major catechin component in green tea, but it shows strong biological activity in some aspects, including apoptosis, cell growth inhibition, and membrane transport system in various cells. We previously reported that ECG induces activating transcription factor 3 (ATF3), which is involved in pro-apoptosis in HCT-116 cells. In this report, we present a molecular mechanism by which ECG induces ATF3 expression at the transcriptional level. We found that Sp3 contributed to the basal expression of the ATF3 gene, whereas EGR-1 played an important role in ECG-induced ATF3 expression in HCT-116 cells, as assessed by EMSA and co-transfection experiments. These results suggested that EGR-1, a tumour suppressor protein, could substantiate ECG's role of ATF3 expression in human colorectal cancer cells. We also found that pro-oxidant activity of ECG contributed to ECG-induced ATF3 expression.

Growth inhibition and apoptosis by (-)-epicatechin gallate are mediated by cyclin D1 suppression in head and neck squamous carcinoma cells.

In recent studies, green tea components have been shown to induce cell growth arrest and apoptosis in head and neck squamous cell carcinoma (HNSCC) cells. In this report, we have investigated the effects of epicatechin gallate (ECG), one of the catechins in green tea, on anti-cancer activity in vitro. We found that cyclin D1 was highly expressed in HNSCC cells, and ECG suppressed 90% of cyclin D1 expression in SCC7 cells. We have also evaluated the effect of ECG on cell growth and apoptosis, showing that ECG (50 microM) exhibited a significant inhibition (50%) on the growth of SCC7 cells via G1 cell cycle arrest. ECG suppressed cyclin D1 in SCC7 cells in a dose- and time-dependent manner, and the suppression of the beta-catenin pathway by ECG is one of the mechanism to facilitate ECG-induced cell growth arrest. These results suggest that ECG has a potential usage as a chemopreventive agent in HNSCC.