Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer.

Niclosamide effectively downregulates androgen receptor variants (AR-Vs) for treating enzalutamide and abiraterone-resistant prostate cancer. However, the poor pharmaceutical properties of niclosamide due to its solubility and metabolic instability have limited its clinical utility as a systemic treatment for cancer. A novel series of niclosamide analogs was prepared to systematically explore the structure-activity relationship and identify active AR-Vs inhibitors with improved pharmaceutical properties based on the backbone chemical structure of niclosamide.

Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis.

Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical.

Maximizing Mentoring: Enhancing the Impact of Mentoring Programs and Initiatives Through the Center for the Advancement of Teaching and Faculty Development at Xavier University of Louisiana.

The Center for the Advancement of Teaching and Faculty Development (CAT+FD) at Xavier University of Louisiana (Xavier) is the stage for a unique model for multiple levels of mentor training and mentoring. The model is made up of four essential components that are necessary to enhance the outcomes of any mentoring initiatives. First, the Institution must be committed to supporting mentoring intitiatives with institutional resources and maintaining a culture that promotes the importance of mentoring for institutional success.

Phytochemicals: Current strategies for treating breast cancer.

Females with early-stage metastatic, estrogen-dependent breast cancer are generally treated with surgery, radiation and chemotherapy, or with more targeted approaches such as aromatase inhibitors (anastrozole or letrozole) or anti-estrogens (tamoxifen). Despite widespread successful usage of these agents for the treatment of breast cancer, resistance, tumor relapse and metastasis remain the principal causes of mortality for patients with breast cancer. While numerous groups have made major contributions toward an improved understanding of resistance mechanisms, the currently insufficient grasp of the most critical pathways involved in resistance is evident in the inability to adequately treat and drastically improve patient outcomes in females with hormone-refractory breast cancer, including triple negative breast cancer.

Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.

There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these molecular interactions impedes pancreatic cancer cell growth as well as reduces fibrosis in a preclinical animal model.

KDAC8 with High Basal Velocity Is Not Activated by N-Acetylthioureas.

Lysine deacetylases (KDACs) are enzymes that reverse the post-translational modification of lysine acetylation. Recently, a series of N-acetylthioureas were synthesized and reported to enhance the activity of KDAC8 with a fluorogenic substrate. To determine if the activation was general, we synthesized three of the most potent N-acetylthioureas and measured their effect with peptide substrates and the fluorogenic substrate under multiple reaction conditions and utilizing two enzyme purification approaches.

Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1.

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT).

Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core.

Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells.

Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e.

Weak C-H···X (X = O, N) hydrogen bonds in the crystal structure of dihydroberberine.

Dihydroberberine (systematic name: 9,10-dimethoxy-6,8-dihydro-5H-1,3-dioxolo[4,5-g]isoquinolino[3,2-a]isoquinoline), C20H19NO4, a reduced form of pharmacologically important berberine, crystallizes from ethanol without interstitial solvent. The molecule shows a dihedral angle of 27.94 (5)° between the two arene rings at the ends of the molecule, owing to the partial saturation of the inner quinolizine ring system.

The chalcone derivative (E)-1-(4-fluoro-phen-yl)-3-(4-hy-droxy-3-meth-oxy-phen-yl)prop-2-en-1-one monohydrate.

The title compound, C16H13FO3·H2O, has a cis disposition of the carbonyl and olefin bonds about the enone single bond. The arene rings are inclined to one another by 10.05 (6) Å.

Celecoxib and Bcl-2: emerging possibilities for anticancer drug design.

Celecoxib is a multifaceted drug with promising anticancer properties. A number of studies have been conducted that implicate the compound in modulating the expression of Bcl-2 family members and mitochondria-mediated apoptosis. The growing data surrounding the role of celecoxib in the regulation of the mitochondrial death pathway provides a platform for ongoing debate.

Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells.

Daidzein (1) is a natural estrogenic isoflavone. We report here that 1 can be transformed into anti-estrogenic ligands by simple alkyl substitutions of the 7-hydroxyl hydrogen. To test the effect of such structural modifications on the hormonal activities of the resulting compounds, a series of daidzein analogues have been designed and synthesized.

Glyceollin I enantiomers distinctly regulate ER-mediated gene expression.

Glyceollins are pterocarpan phytoalexins elicited in high concentrations when soybeans are stressed. We have previously reported that the three glyceollin isomers (GLY I-III) exhibit antiestrogenic properties, which may have significant biological effects upon human exposure. Of the three isomers, we have recently shown that glyceollin I is the most potent antiestrogen.

Glyceollin I, a novel antiestrogenic phytoalexin isolated from activated soy.

Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen.

Molecular effects of soy phytoalexin glyceollins in human prostate cancer cells LNCaP.

Glyceollins are soy-derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexin, glyceollins, on human prostate cancer cell LNCaP to further elucidate its potential effects on prostate cancer prevention.

Identification of the potent phytoestrogen glycinol in elicited soybean (Glycine max).

The primary induced isoflavones in soybean, the glyceollins, have been shown to be potent estrogen antagonists in vitro and in vivo. The discovery of the glyceollins' ability to inhibit cancer cell proliferation has led to the analysis of estrogenic activities of other induced isoflavones. In this study, we investigated a novel isoflavone, glycinol, a precursor to glyceollin that is produced in elicited soy.