Showing papers by "David Heber published in 2005"

In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice

Abstract: Pomegranate (Punica granatum L.) fruits are widely consumed as juice (PJ). The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA). Punicalagin is the major antioxidant polyphenol ingredient in PJ. Punicalagin, EA, a standardized total pomegranate tannin (TPT) extract and PJ were evaluated for in vitro antiproliferative, apoptotic and antioxidant activities. Punicalagin, EA and TPT were evaluated for antiproliferative activity at 12.5-100 microg/ml on human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, 22Rv1) tumor cells. Punicalagin, EA and TPT were evaluated at 100 microg/ml concentrations for apoptotic effects and at 10 microg/ml concentrations for antioxidant properties. However, to evaluate the synergistic and/or additive contributions from other PJ phytochemicals, PJ was tested at concentrations normalized to deliver equivalent amounts of punicalagin (w/w). Apoptotic effects were evaluated against the HT-29 and HCT116 colon cancer cell lines. Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 microg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.

Total Cranberry Extract vs. its Phytochemical Constituents: Antiproliferative and Synergistic Effects against Human Tumor Cell Lines

Abstract: Cranberries (Vaccinium macrocarpon Ait.) are an excellent dietary source of phytochemicals that include flavonol glycosides, anthocyanins, proanthocyanidins (condensed tannins), and organic and phenolic acids. Using C-18 and Sephadex Lipophilic LH-20 column chromatography, HPLC and tandem LC-ES/MS, we have analyzed, quantified and separated total cranberry extract (TCE) into fractions enriched in sugars, organic acids, total polyphenols, proanthocyanidins and anthocyanins (39.4, 30.0, 10.6, 5.5, 1.2% composition, respectively). Using a luminescent ATP cell viability assay, the antiproliferative effects of TCE (200 g/mL) vs. all fractions were evaluated against human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, RWPE-2, 22Rv1) cancer cell lines. The total polyphenol fraction was the most active fraction against all cell lines with 96.1 and 95% inhibition of KB and CAL27 oral cancer cells, respectively. For the colon cancer cells, the antiproliferative activity of this fraction was greatest against HCT116 (92.1%) than HT-29 (61.1%), SW480 (60%) and SW620 (63%). TCE and all fractions, showed 50% antiproliferative activity against prostate cancer cells with total polyphenols being the most active fraction (RWPE-1, 95%; RWPE-2, 95%; 22Rv1, 99.6%). Cranberry sugars (78.8 g/mL) did not inhibit the proliferation of any cancer cell lines. The enhanced antiproliferative activity of total polyphenols compared to TCE and its individual phytochemicals suggests synergistic or additive antiproliferative interactions of the anthocyanins, proanthocyanidins and flavonol glycosides within the cranberry extract.

Identification of phenolic compounds in strawberries by liquid chromatography electrospray ionization mass spectroscopy

Abstract: Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, anticancer, antiatherosclerotic and anti-neurodegenerative properties. Identification of food phenolics is necessary since their nature, size, solubility, degree and position of glycosylation and conjugation influence their absorption, distribution, metabolism and excretion in humans. Freeze-dried whole strawberry fruit powder and strawberry fruit extracts were analyzed by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) methods. Phenolics were identified as ellagic acid (EA), EA-glycosides, ellagitannins, gallotannins, anthocyanins, flavonols, flavanols and coumaroyl glycosides. The anthocyanidins were pelargonidin and cyanidin, found predominantly as their glucosides and rutinosides. The major flavonol aglycons were quercetin and kaempferol found as their glucuronides and glucosides. LC-ESI-MS/MS methods differentiated EA from quercetin conjugates since both aglycons have identical molecular weights (302 g/mol). The identification of strawberry phenolics is necessary to generate standardized materials for in vitro and in vivo studies and for the authentication of strawberry-based food products.

Phytoestrogens induce differential estrogen receptor alpha- or Beta-mediated responses in transfected breast cancer cells.

Abstract: Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor a (ERα) and human estrogen receptor β (ERβ). Nine phytoestrogens were tested for their ability to transactivate ERα or ERβ at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERα or ERβ, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17β-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERα- and ERβ-induced transcription, with an up to 100-fold stronger activation of ERβ. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17β-estradiol, the a...

Inhibition of prostate cancer cell growth by an avocado extract: role of lipid-soluble bioactive substances.

Abstract: Although the avocado is known as a rich source of monounsaturated fatty acids, there has been far less attention given to its content of other bioactive substances including carotenoids, which might contribute to cancer preventive properties similar to those attributed to other fruits and vegetables. The yellow-green color of the avocado prompted us to study the carotenoid content of this fruit using established methods in our laboratory. The California Hass avocado ( Persea americana Mill.) was selected for study, because it is the most commonly consumed variety in the southwest United States. These avocados were found to contain the highest content of lutein among commonly eaten fruits as well as measurable amounts of related carotenoids (zeaxanthin, α-carotene, and β-carotene). Lutein accounted for 70% of the measured carotenoids, and the avocado also contained significant quantities of vitamin E. An acetone extract of avocado containing these carotenoids and tocopherols was shown to inhibit the growth of both androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines in vitro. Incubation of PC-3 cells with the avocado extract led to G 2 /M cell cycle arrest accompanied by an increase in p27 protein expression. Lutein alone did not reproduce the effects of the avocado extract on cancer cell proliferation. In common with other colorful fruits and vegetables, the avocado contains numerous bioactive carotenoids. Because the avocado also contains a significant amount of monounsaturated fat, these bioactive carotenoids are likely to be absorbed into the bloodstream, where in combination with other diet-derived phytochemicals they may contribute to the significant cancer risk reduction associated with a diet of fruits and vegetables.

Bioavailability and antioxidant effect of epigallocatechin gallate administered in purified form versus as green tea extract in healthy individuals.

Abstract: Tea polyphenols have strong in vitro antioxidant activity. Due to their limited bioavailability, however, their contribution to in vivo antioxidant activity may depend on the form of administration. A human intervention study was performed to evaluate the bioavailability and antioxidant capacity of (-)-epigallocatechin-3-gallate (EGCG) administered as a single large dose in the form of either purified EGCG or as green tea extract (Polyphenon E). Plasma concentrations of tea polyphenols were determined by high-performance liquid chromatography (HPLC) analysis combined with coulometric array electrochemical detection (ECD). We found no differences in plasma EGCG concentrations and trolox equivalents determined by the trolox equivalent antioxidant capacity assay after administration of either form of EGCG. However, we found that the plasma antioxidant activity was significantly affected by changes in the plasma urate concentration, which may have interfered with the effect of tea polyphenols on the antioxidant activity. In addition, lymphocyte 8-hydroxydeoxyguanosine to deoxyguanosine (8-OHdG/10(6)dG) ratios were determined by HPLC with ECD. The 8-OHdG/10(6)dG ratios did not change significantly during the 24 h following both EGCG interventions but correlated significantly within individuals determined during the two interventions separated by 1 week. In summary, changes in plasma uric acid due to dietary intake were significantly correlated to the plasma antioxidant activity and exerted a stronger influence on the plasma antioxidant activity compared with the EGCG intervention. In future studies of dietary effects on the plasma antioxidant capacity, changes in plasma uric acid will need to be closely monitored.

Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein.

Abstract: Achieving significant weight loss and glycemic control in diabetic patients remains a challenging task. This study compared the effects of a soy-based meal replacement (MR) plan vs an individualized diet plan (IDP; as recommended by the American Diabetes Association) on weight loss and metabolic profile. A total of 104 subjects were randomized prospectively to the two treatments for a total of 12 months. In all, 77 of the 104 subjects completed the study. Percentage weight loss in MR group (4.57±0.81%) was significantly greater (P<0.05) than in IDP group (2.25±0.72%). Fasting plasma glucose was significantly reduced in MR group (126.4±4.9 mg/dl) compared with IDP group (152.5±6.6 mg/dl, P<0.0001) at 6 months but not at 12 months. Controlling for baseline levels, hemoglobin Alc level improved by 0.49±0.22% for those receiving MR when compared to IDP group (P<0.05). A greater number of subjects in MR group reduced their use of sulfonylureas (P<0.0001) and metformin (P<0.05) as compared to IDP group. High-sensitivity C-reactive protein (hs-CRP) decreased −26.3% (P=0.019) in MR group compared to −7.06% (P=0.338) in IDP group at 6 months. Similar changes were observed at 12 months with MR groups, with hs-CRP decreasing by −25.0% (P=0.019) compared to −18.7% (P=0.179) in IDP group. This study demonstrates that MR is a viable strategy for weight reduction in diabetic patients, resulting in beneficial changes in measures of glycemic control and reduction of medications.

Characterization of human fibrocytes as circulating adipocyte progenitors and the formation of human adipose tissue in SCID mice

Abstract: An increase in fat mass associated with obesity results from recruitment and differentiation of adipocyte progenitor cells. The precise origin of these cells is unknown, although accumulating evidence suggests that circulating stem cells can differentiate into cells of mesenchymal lineage. It is currently unclear whether a progenitor adipocyte population exists in circulation. One potential candidate is the fibrocyte, which may represent a common progenitor cell for several mesenchymal lineages. We demonstrate that these circulating progenitors become adipocytes when cultured under adipogenic conditions, with intracellular lipids accumulation and up-regulation of proteins specific for adipocyte differentiation, including leptin, PPARgamma, and FABP4. cDNA microarray analysis revealed gene clusters that were differentially regulated during adipogenesis of fibrocytes, which were similar to visceral and subcutaneous adipose tissue preadipocyte-to-adipocyte differentiation. Moreover, these progenitors engrafted and formed human adipose tissue following injection into SCID mice. Although fibrocytes express an array of chemokine receptors, we observed an up-regulation of CCR2 expression following fibrocytes differentiation into adipocytes, which was associated with increased chemotactic response to CCL2. This paradigm supports the notion that elevated CCL2 levels in visceral adipose tissue associated with Metabolic Syndrome is a chemotactic niche, whereby fibrocytes can home to and differentiate into adipocytes to perpetuate its tissue formation.

Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population

Abstract: The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population-based case-control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in-person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR-RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] = 0.34-1.01). Dose-response relationship was shown (p-trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI = 1.02-4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI = 1.62-12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI = 0.88-6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested.

Risk of prostate cancer in a randomized clinical trial of calcium supplementation.

Abstract: Background: In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue. Methods: We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels. Results: After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk. Conclusion: In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.

Low-Fat High-Fiber Diet Decreased Serum and Urine Androgens in Men

Abstract: To validate our hypothesis that reduction in dietary fat may result in changes in androgen metabolism, 39 middle-aged, white, healthy men (50-60 yr of age) were studied while they were consuming their usual high-fat, low-fiber diet and after 8 wk modulation to an isocaloric low-fat, high-fiber diet. Mean body weight decreased by 1 kg, whereas total caloric intake, energy expenditure, and activity index were not changed. After diet modulation, mean serum testosterone (T) concentration fell (P < 0.0001), accompanied by small but significant decreases in serum free T (P = 0.0045), 5 alpha-dihydrotestosterone (P = 0.0053), and adrenal androgens (androstendione, P = 0.0135; dehydroepiandrosterone sulfate, P = 0.0011). Serum estradiol and SHBG showed smaller decreases. Parallel decreases in urinary excretion of some testicular and adrenal androgens were demonstrated. Metabolic clearance rates of T were not changed, and production rates for T showed a downward trend while on low-fat diet modulation. We conclude that reduction in dietary fat intake (and increase in fiber) results in 12% consistent lowering of circulating androgen levels without changing the clearance.

Inhibition of Growth of Streptococcus mutans, Methicillin-Resistant Staphylococcus aureus, and Vancomycin-Resistant Enterococci by Kurarinone, a Bioactive Flavonoid Isolated from Sophora flavescens

Abstract: Infectious diseases caused by pathogenic bacteria have been the leading cause of morbidity and mortality in human history. The discovery of the antibacterial compound from the mold Penicillium notatum by Alexander Fleming led to the development of antibiotics, which are still the main weapons for combating the deadly bacterial infections at the present time. However, over 60 years of application of antibiotics leads to the development of antibiotic resistance of many bacterial pathogens. Consequently, bacterial infections have again become the most common and deadly causes of human diseases. Two of the most lethal hospital infections are caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) (10). Furthermore, Streptococcus mutans-associated tooth decay is one of the most prevalent and costly infectious diseases in the United States (4, 11; http://www.surgeongeneral.gov/library/oralhealth/). The emergence of both “new pathogens” and resistant strains from “old pathogens” demands new antibacterial compounds to deal with this crisis. Given the fact that most commonly used antibiotics are isolated from microorganisms, it is important to search for new antibacterial compounds from new bio-resources. Chinese medicinal herbs are logical choices due to their proven ability to treat microbial infections. In traditional Chinese medicine (TCM) practice, a group of herbs has been widely used for a specific therapeutic application defined as Qing Re Jie Du (), or “alleviating heat and relieving the symptoms caused by toxins” (2, 3). Many herbs in this category have been found to have antimicrobial activities (2, 3). Recently, we conducted a systematic screen of herbs with Qing Re Jie Du function for the inhibitory activities against S. mutans, the primary etiological agent for dental caries and other pathogens (1), and found that the extract made from Sophora flavescens contains a potent bioactivity against S. mutans, MRSA, and VRE. S. flavescens is a perennial shrub found in Northeast Asia (Fig. ​(Fig.1A).1A). It grows in sandy soils on mountain slopes or river valleys. In spring or autumn, the roots are collected, cleaned, sliced, and air-dried. The processed root of S. flavescens is also known as “Ku Shen,” which means “a precious medicinal root with bitter taste” (Fig. ​(Fig.1B).1B). In more than 1,000 years of TCM practice, it has being used to treat pyretic and analgesic symptoms (http://www.itmonline.org/arts/sophora.htm). Although a variety of bioactive compounds have been recently isolated from S. flavescens for the treatment of inflammation, cancer, and cardiovascular disorders (5, 13), the knowledge about its antibacterial potential is limited (7). FIG. 1. Sophora flavescens (A) and its dried roots (Ku Shen) (B) used in TCM application. To study the active antimicrobial component(s) in S. flavescens, the following procedures were followed. First, an extract of S. flavescens was prepared according to a previously published extraction method (1), and its MIC against S. mutans was determined with a protocol recommended by the National Committee of Clinical Laboratory Standards (NCCLS) (9) (Table ​(Table1).1). Following the bioassay, the extract was then chromatographed over silica gel (100- to 200-mesh; Selecto, Georgia), and eluted with a hexane:ethyl gradient acetate. Equal volumes of the eluted solutions were collected, dried by evaporation, and subjected to the antimicrobial assay to track down the most active fraction(s). Following the bioassay, the chemical composition of active fractions was then analyzed by thin-layer chromatography and high-performance liquid chromatography (HPLC). The result indicated that the most active fraction contains ∼80% of the active compound. Further purification was performed on semipreparative HPLC equipment (600E system controller and 996 photodiode array detector; Waters, Milford, MA) equipped with a reverse-phase C18 column (7.8 by 300 mm). The homogeneity of the purified active compound (>95%) was established by both HPLC profiles (data not shown) and subsequent 1H nuclear magnetic resonance (NMR) spectra (500 MHz) (Fig. ​(Fig.22). FIG. 2. Proton-NMR spectrum of purified kurarinone. TABLE 1. Susceptibility of S. mutans, MRSA, and VRE to antimicrobial compounds and kurarinone The purified compound was then analyzed by mass spectrometer and NMR spectroscopy (1H and 13C), respectively. Based on the extensive one- and two-dimensional (1D and 2D)NMR spectroscopic interpretation and mass spectrometer analysis (data not shown), we concluded that the isolated active compound is kurarinone, a known compound isolated from S. flavescens (5, 7, 8, 13). Kurarinone is a flavonoid with a lavandulyl side chain, and its chemical structure is illustrated in Fig. ​Fig.33. FIG. 3. Kurarinone (A) and its time- and dose-dependent bactericidal effect against S. mutans (B). The chemical structure of kurarinone was elucidated on the basis of extensive 1D and 2D NMR spectroscopic interpretation. The killing effect of kurarinone was determined ... Several bioactivities of kurarinone have been previously reported, including antifungal activities against Candida albicans and Cladosporium cucumerinum(12), antimalarial activity (6), cytotoxic activity against human tumor cells (myeloid leukemia HL-60 cells) (5), and COX-1 inhibitory activity (5). At the current stage, the molecular mechanisms of its action in both pathogens and mammalian cells are largely unknown. In this study, a strong antibacterial activity of kurarinone was detected. Its MICs against S. mutans and multidrug-resistant strains (MRSA and VRE) are at the same level (2 μg/ml) (Table ​(Table1).1). Time- and dose-dependent bactericidal effects of kurarinone against S. mutans (Fig. ​(Fig.3B),3B), MRSA, and VRE (data not shown) were also detected. These data suggested a potential application of kurarinone for the treatment of diseases or conditions associated with S. mutans, MRSA, and VRE.

Green Tea Extract Modulates Actin Remodeling via Rho Activity in an In vitro Multistep Carcinogenic Model

Abstract: Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent.

Analysis of weight loss outcomes using VLCD in black and white overweight and obese women with and without metabolic syndrome

Abstract: To evaluate the efficacy of very low calorie diet (VLCD) in black and white obese women. Changes in weight, metabolic profile, and body composition are assessed. Patients are enrolled in a self-paid, university-based, outpatient weight loss program. All are prescribed VLCD (500–800 Cal/day), an exercise regimen, and group behavioral counseling. Black and white patients are matched for age, weight, body mass index, and by metabolic syndrome (MS) status. A total of 304 black and white women (152 in each group) were included the analysis. Approximately 40% of patients had MS (white women: 39.5%; black women: 41.2%). Mean baseline weights were similar. After 12 weeks, weight reduction of 9.97% was seen in white women and 9.02% drop was seen in black women (both P<0.0001). However, the degree of weight change was not different between the groups (P=0.244). Marked improvements in fasting glucose, total cholesterol, LDL, triglyceride, and blood pressures (BP) were observed (all P<0.01); however, no difference between cohorts were seen. Patients with MS had higher baseline weight, BP, glucose and triglyceride levels when compared to patients without MS (all P<0.01). Significant reductions in % body fat were seen in white and black patients, independent of MS status. Obese patients, independent of race, were able to achieve significant weight loss when enrolled in a structured outpatient program. Weight loss significantly correlated with all aspects of MS. Our results suggest that differences seen in past studies may be influenced by socioeconomic and behavioral factors rather than differences in physiological response to dieting.

Plasma clearance of lovastatin versus chinese red yeast rice in healthy volunteers.

Abstract: Objectives: It is now accepted that inhibition of cholesterol biosynthesis is effective in the primary and secondary prevention of heart disease. However, the perceived side-effects on muscle and l...

Rabdosia rubescens inhibits breast cancer growth and angiogenesis

Abstract: Investigators have shown that PC-SPES is a potent herbal mixture which has often been used by prostate cancer patients. In this study, we examined the inhibitory effects of certain individual components of PC-SPES on the in vitro proliferation of the human breast cancer cells MDA-MB231 and the human umbilical vein endothelial cells (HUVEC). Our data showed that individual components of PC-SPES had varying suppressive effects on cellular proliferation, and that Rabdosia rubescens appeared to be the most potent agent in these assays. Apoptosis was up-regulated by Rabdosia rubescens, as seen in the caspase-9 and TUNEL assays. These effects may be mediated via both the MAPK (mitogen-activated protein kinase) and the Akt kinase pathways. In mouse experiments, the extract from Rabdosia rubescens suppressed breast cancer xenograft size and decreased the tumor vessel density. We conclude that Rabdosia rubescens may potentially be used to treat or prevent breast cancer, and that the extract from this herbal source deserves further studies.

Novel interactions of vitamin E and estrogen in breast cancer

Abstract: The prevention of breast cancer through dietary modification is an active area of clinical and epidemiological research It has been proposed that dietary supplementation of vitamin E may reduce a woman's risk of developing breast cancer However, the exact mechanism remains unknown alpha-Tocopherol is the most biologically active form of vitamin E We investigated the effect of vitamin E (alpha-tocopherol) on breast cancer cell growth A dose-dependent inhibition of cell proliferation was found in estrogen receptor (ER)-positive cells showing a potent suppression of growth at 100 microM vitamin E in MCF-7 (53%) and T47D (75%) cells Vitamin E reduced significantly the response of both cell lines to estrogen (10 nM), and cell proliferation was decreased in MCF-7 and T47D cells by 69% and 84%, respectively No growth inhibition was observed when cells were grown in the absence of estrogen Vitamin E altered and decreased the growth inhibition induced by tamoxifen (10 microM) in MCF-7 (33%) and T47D (54%) cells In addition, the immunostaining of ER of MCF-7 cells was reduced by 30% in the presence of vitamin E, suggesting an effect of vitamin E on the expression of ER This provides evidence that vitamin E may inhibit ER-positive cell growth by altering the cellular response to estrogen

The synthetic furanonaphthoquinone induces growth arrest, apoptosis and differentiation in a variety of leukaemias and multiple myeloma cells.

Abstract: 2-methyl-naphtho[2,3-b]furan-4,9-dione (FNQ3), a synthetic analogue of the quinone kigelinone, has demonstrated a real potential for use in the treatment of a variety of solid tumours. Unlike other quinones, such as mitomycin-C and adriamycin, the cytotoxicity of FNQ3 is often 10- to 14-fold more potent towards the tumour cells than their normal counterparts. We report, for the first time, that the drug had activity against a broad spectrum of leukaemias and multiple myeloma cells. It decreased the growth of acute myeloid leukaemia (AML) and multiple myeloma cell lines in a dose-dependent fashion (50% inhibitory concentration approximately 1.25 microg/ml against most of the leukaemia cell lines). This dose apparently initiated mitochondrial collapse as measured by depolarisation of the mitochondrial membrane. FNQ3 potentiated the differentiation of HL-60 myeloid cells in the presence of either 1alpha, 25(OH)(2) dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or all-trans-retinoic acid (ATRA). FNQ3 inhibited the proliferation of primary AML cells while inducing apoptosis. Eleven of 14 (79%) AML marrow samples had a prominent decrease in their clonogenic growth when cultured in the presence of the drug. In summary, this drug has growth inhibitory, apoptotic and differentiative effects against myeloid leukaemias and multiple myeloma cells. FNQ3 may represent a new therapeutic approach to these malignancies.

Identification of botanicals and potential contaminants through RFLP and sequencing.

Abstract: Botanical supplements for health enhancement are being increasingly used in the United States, but no safeguards are formally in place to ensure that they are not contaminated with non-efficacious or potentially harmful plant material. A molecular approach, which allows the authentication of botanical ingredients and detection of contaminating plant material by analyzing the ITS-1 region by PCR-RFLP and subsequent sequencing, is described. When using starting material from which DNA can be obtained, this method has the potential for identifying both primary and contaminating plant material in botanical dietary supplements.

Rapid large scale purification of ellagitannins from pomegranate husk, a by-product of the commercial juice industry - eScholarship

Abstract: Pomegranate (Punica granatum L.) fruits are widely consumed fresh and in the forms of juice, concentrate, wine and jam. Pomegranate fruit husk is a rich source of hydrolyzable tannins called ellagitannins (ETs). During processing methods in the commercial pomegranate juice (PJ) industry, ETs are extracted from the fruit husk in significant quantities into the juice. Pomegranate husk, a by-product of the PJindustry, is therefore an inexpensive and abundant source of ETs which are present in PJ. Previous methods to isolate pomegranate ETs included labor intensive and time-consuming solid phase extractions by column chromatography (C-18, polyamides, cellulose, Sephadex Lipophilic LH-20, Diaion HP20) and/or use of specialized instruments such as preparative-high performance liquid chromatography (HPLC). We have used an Amberlite XAD-16 resin vacuum-aspirated column to rapidly purify an aqueous extract of pomegranate husk to afford total pomegranate tannins (TPT) in substantial yields (58-60 g TPT/Kg husk; time <1h). Using analytical HPLC, NMR and tandem LC-ES/MS, evaluation of TPT showed that it contains the major fruit husk ET, punicalagin (85% w/w), and ellagic acid (EA; 1.3% w/w) as well as unquantified amounts of punicalin and EA glycosides (hexoside, rhamnoside and pentoside). Since ETs are reported to show potent antioxidant, antiatherosclerotic and anticancer activities, this method can be used for the large-scale production of TPT for future in vitro and in vivo biological studies. This method is practical for industrial applications and could provide a low-cost means to use a currently underutilized food by-product to develop phytoceuticals with potential health benefits or to develop products for use in the cosmetic and food biopreservative industries.