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  • Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications. 22662208

    Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER)-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ERα expression for effective treatment of ERα-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ERα-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ERα expression. The combination of 20 µg/mL GTPs and 5 µM SFN was found to be the optimal dose of ERα-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ERα expression was consistently correlated with ERα promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP) analysis of the ERα promoter revealed that GTPs and SFN altered the binding of ERα-transcriptional co-repressor complex thereby contributing to ERα-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens.
    Document Type:
    Reference
    Product Catalog Number:
    17-371
    Product Catalog Name:
    EZ-ChIP™

  • Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived s ... 22510402

    The development of osteochondral tissue engineered interfaces would be a novel treatment for traumatic injuries and aging associated diseases that affect joints. This study reports the development of a bilayered scaffold, which consists of both bone and cartilage regions. On the other hand, amniotic fluid-derived stem cells (AFSCs) could be differentiated into either osteogenic or chondrogenic cells, respectively. In this study we have developed a bilayered scaffolding system, which includes a starch/polycaprolactone (SPCL) scaffold for osteogenesis and an agarose hydrogel for chondrogenesis. AFSC-seeded scaffolds were cultured for 1 or 2 weeks in an osteochondral-defined culture medium containing both osteogenic and chondrogenic differentiation factors. Additionally, the effect of the presence or absence of insulin-like growth factor-1 (IGF-1) in the culture medium was assessed. Cell viability and phenotypic expression were assessed within the constructs in order to determine the influence of the osteochondral differentiation medium. The results indicated that, after osteogenic differentiation, AFSCs that had been seeded onto SPCL scaffolds did not require osteochondral medium to maintain their phenotype, and they produced a protein-rich, mineralized extracellular matrix (ECM) for up to 2 weeks. However, AFSCs differentiated into chondrocyte-like cells appeared to require osteochondral medium, but not IGF-1, to synthesize ECM proteins and maintain the chondrogenic phenotype. Thus, although IGF-1 was not essential for creating osteochondral constructs with AFSCs in this study, the osteochondral supplements used appear to be important to generate cartilage in long-term tissue engineering approaches for osteochondral interfaces. In addition, constructs generated from agarose-SPCL bilayered scaffolds containing pre-differentiated AFSCs may be useful for potential applications in regeneration strategies for damaged or diseased joints.
    Document Type:
    Reference
    Product Catalog Number:
    MAB1330
    Product Catalog Name:
    Anti-Collagen Type II Antibody, clone COLL-II

  • Polyphenol rich botanicals used as food supplements interfere with EphA2-ephrinA1 system. 21742039

    The Eph tyrosine kinase receptors and their ephrin ligands play a central role in several human cancers and their deregulated expression or function promotes tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE) have been recently found to inhibit Eph-kinase phosphorylation. In order to evaluate the potential contribution of edible and medicinal plants on EphA2-ephrinA1 modulation, 133 commercially available plant extracts used as food supplements, essential and fixed oils were screened with an ELISA-based binding assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in a dose-dependent manner (IC(50) 0.83-24μg/ml). Functional studies on PC3 prostate adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc-induced EphA2-phosphorylation at non-cytotoxic concentrations (IC(50) 0.31-11.3μg/ml) without interfering with EGF-induced EGFR activation, suggesting a specific effect. These findings could furnish an interesting starting point regarding the potential relationship between diet, edible plant secondary metabolites and Eph-ephrin system, suggesting their possible involvement in cancer development modulation.
    Document Type:
    Reference
    Product Catalog Number:
    AG714
    Product Catalog Name:
    Human IgG, Fc Fragment

  • Prostate-specific natural health products (dietary supplements) radiosensitize normal prostate cells. 20159364

    PURPOSE: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. METHODS AND MATERIALS: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity was assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX. RESULTS: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2 microg/mL], Trinovin [10 microg/mL], and Prostate Rx [50 microg/mL]). However, both Trinovin (10 microg/mL) and Prostate Rx (6 microg/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. CONCLUSION: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.
    Document Type:
    Reference
    Product Catalog Number:
    05-636
    Product Catalog Name:
    Anti-phospho-Histone H2A.X (Ser139) Antibody, clone JBW301

  • The effect of production level on feed intake, milk yield, and endocrine responses to two fatty acid supplements in lactating cows. 16230708

    Animal responses to dietary treatment may interact with metabolic state, which differs for cows across a wide range of milk yield. Responses to dietary saturated vs. unsaturated fatty acid (FA) supplement was evaluated using 32 multiparous Holstein cows arranged in a crossover design with 14-d periods. Treatments were 2.5% FA from unsaturated FA (calcium salts of palm FA) or saturated FA (prilled, hydrogenated free FA). Unsaturated FA treatments decreased dry matter intake (0.8 kg/d) and time spent ruminating (25 min/d) compared with saturated FA treatment. Treatments did not differ in milk or 3.5% fat-corrected milk yield. Intake and milk yield responses were not related to milk yield across cows. Saturated FA treatment increased milk protein and lactose concentrations, but treatment did not affect yield of milk components. Saturated FA treatment increased insulin over 25% and decreased nonesterified FA nearly 20% with no effect on plasma somatotropin, glucose, or beta-hydroxybutyrate concentrations. Milk protein concentration and yield responses to treatment were positively correlated with pretrial fat-corrected milk yield. Milk protein response was not related to insulin response, supporting the importance of insulin sensitivity in control of milk protein synthesis. Unsaturated FA treatment decreased dry matter intake and rumination time compared with saturated FA treatment, consistent with reports of unsaturated fat increasing satiety and decreasing gut motility. Decreased milk protein synthesis by fat supplementation may be related to FA saturation and milk yield of cows.
    Document Type:
    Reference
    Product Catalog Number:
    GL-32K
    Product Catalog Name:
    Glucagon RIA