Van Breemen: Core 2; Bioassay Core (Bolton)

$227,872P50FY2016ATNIH

University Of Illinois At Chicago, Chicago IL

Investigators

Linked publications, trials & patents

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Abstract

Bioassay Core C will provide support for all Projects/Cores with a well-characterized array of validated, robust and efficient bioassays with the following specific aims: Aim 1. Evaluate botanicals/compounds for stimulation of resilience/chemopreventive pathways. We will analyze the antioxidative activity, the NAD(P)H:quinone oxidoreductase 1 (NQO1) inducing properties, the anti-inflammatory activity, and aromatase inhibiting properties of the extracts/compounds. Extracts/compounds active in the NQO1 assay will be analyzed in the antioxidative response element luciferase assay and in the glutathione-S-transferase induction assay. The induction of several Phase I metabolism enzymes is regulated by the xenobiotic response element (XRE). Inducers of Phase I enzymes interfere with the metabolism of other drugs and endogenous estrogen; therefore, the extracts will also be tested in the XRE-luciferase assay. Aim 2. Evaluate botanicals/compounds for hormonal activity (efficacy). Various bioassays have been developed to evaluate botanicals for estrogenic, progestogeinic, and androgenic activity. The alkaline phosphatase assay (Ishikawa cells) will be employed to test the botanicals for estrogenic/ antiestrogenic activities. Active fractions will be analyzed for estrogen receptor ER? and ER? selectivity, progestin receptor (PR), and androgen receptor (AR) functional activity in luciferase assays in breast cancer cells. Active samples will be tested for ER/PR/AR ligands in competitive radioactive binding assays. These assays will define the hormonal efficacy of botanical dietary supplements used for women's health. Aim 3. Evaluate botanicals for safety and efficacy in vivo. When active extracts/compounds have been identified with Project 1/Core B, in vivo studies to analyze safety, efficacy, distribution and metabolism will be performed with Project 3/Core D. Rat models will be utilized to analyze the extracts/ compounds for safety (necropsy, blood parameters), resilience (induction of detoxification enzymes; NQO1, GST), and efficacy (estrogenic, progestogenic). With these bioassays, Core C directly supports the efforts of the entire Center by establishing active and/or toxic/interfering compounds, thus providing biomarkers for standardization of new botanicals for women's health.

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