A5003229513- Nuclear Receptors and Signaling
- Angiogenesis and VEGF in Cancer
- Peroxisome Proliferator-Activated Receptors
- Cancer Treatment and Pharmacology
- Macrophage Migration Inhibitory Factor
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Natural product bioactivities and synthesis
- Microtubule and mitosis dynamics
- Inflammatory mediators and NSAID effects
- Cancer-related molecular mechanisms research
- Lipid metabolism and disorders
- Sphingolipid Metabolism and Signaling
- Lung Cancer Treatments and Mutations
- Plant biochemistry and biosynthesis
- Synthesis and Characterization of Heterocyclic Compounds
- Hippo pathway signaling and YAP/TAZ
- Organic Chemistry Cycloaddition Reactions
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Pharmacological Effects of Natural Compounds
- Retinoids in leukemia and cellular processes
- Helicobacter pylori-related gastroenterology studies
Pfizer (United States)
2024
Texas A&M University
2006-2023
Texas A&M Health Science Center
2007-2023
Eli Lilly (United States)
2012-2021
Indianapolis Zoo
2015
Heidelberg University
2013
University Hospital Heidelberg
2013
German Cancer Research Center
2013
DKFZ-ZMBH Alliance
2013
Heidelberg University
2013
Abstract There is evidence that specificity proteins (Sp), such as Sp1, Sp3, and Sp4, are overexpressed in tumors contribute to the proliferative angiogenic phenotype associated with cancer cells. Sp4 expressed a panel of estrogen receptor (ER)–positive ER-negative breast cell lines, we hypothesized regulation their expression may be due microRNA-27a (miR-27a), which also these lines has been reported regulate zinc finger ZBTB10 gene, putative Sp repressor. Transfection MDA-MB-231 cells...
Abstract Betulinic acid is a pentacyclic triterpene natural product initially identified as melanoma-specific cytotoxic agent that exhibits low toxicity in animal models. Subsequent studies show betulinic induces apoptosis and antiangiogenic responses tumors derived from multiple tissues; however, the underlying mechanism of action unknown. Using LNCaP prostate cancer cells model, we now decreases expression vascular endothelial growth (VEGF) antiapoptotic protein survivin. The these...
Polyphenols from fruits and vegetables exhibit anticancer properties both in vitro vivo specialty potatoes are an excellent source of dietary polyphenols, including phenolic acids anthocyanins. This study investigated the effects potato phenolics their fractions on LNCaP (androgen dependent) PC-3 independent) prostate cancer cells. Phenolic extracts four cultivars CO112F2-2, PATX99P32-2, ATTX98462-3 ATTX98491-3 organic acid, acid anthocyanin (AF) were used this study. CO112F2-2 cultivar AF...
Abstract Curcumin is the active component of tumeric, and this polyphenolic compound has been extensively investigated as an anticancer drug that modulates multiple pathways genes. In study, 10 to 25 μmol/L curcumin inhibited 253JB-V KU7 bladder cancer cell growth, was accompanied by induction apoptosis decreased expression proapoptotic protein survivin angiogenic proteins vascular endothelial growth factor (VEGF) VEGF receptor 1 (VEGFR1). Because survivin, VEGF, VEGFR1 are dependent on...
Abstract Nerve growth factor–induced Bα (NGFI-Bα, Nur77) is an orphan nuclear receptor with no known endogenous ligands; however, recent studies on a series of methylene-substituted diindolylmethanes (C-DIM) have identified 1,1-bis(3′-indolyl)-1-(phenyl)methane (DIM-C-Ph) and 1,1-bis(3′-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH3) as Nur77 agonists. expressed in several colon cancer cell lines (RKO, SW480, HCT-116, HT-29, HCT-15), we also observed by immunostaining that was overexpressed...
Abstract Background Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors the effects BA have been attributed to its mitochondriotoxicity inhibition multiple pro-oncogenic factors. Previous studies show that induces proteasome-dependent degradation specificity protein (Sp) transcription factors Sp1, Sp3 Sp4 in prostate cells this study focused on mechanism action colon cells. Methods The proliferation apoptosis tumor vivo were determined using standardized assays. Sp...
Abstract Activation of the orphan nuclear receptor TR3/Nur77 (NR4A1) promotes apoptosis and inhibits pancreatic tumor growth, but its endogenous function effects inactivation have yet to be determined. TR3 was overexpressed in human tumors compared with nontumor tissue. Small interfering RNA–mediated knockdown or cell treatment antagonist 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) decreased proliferation, induced apoptosis, expression antiapoptotic genes including Bcl-2...
Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of spatial architecture tissue structure and function. Advancing "transcript-centric" view scRNA-seq analyses is presently restricted by limited resolution proteomics genome-wide techniques to analyze post-translational modifications. Here, combining cell sorting with quantitative proteomics/phosphoproteomics, we established spatially resolved proteome landscape liver endothelium, yielding deep mechanistic insight...
Nur77 is an orphan receptor and a member of the nerve growth factor-I-B subfamily nuclear family transcription factors. Based on results transactivation assays in pancreatic other cancer cell lines, we have now identified for first time agonists typified by 1,1-bis(3-indolyl)-1-(p-anisyl)methane that activate GAL4-Nur77 chimeras expressing wild-type ligand binding domain (E/F) Nur77. In Panc-28 cells, receptor, downstream responses include decreased survival induction death pathways,...
Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic derivative of glycyrrhetinic acid, triterpenoid phytochemical found in licorice extracts. CDODA-Me inhibited growth RKO and SW480 colon cancer cells this was accompanied by decreased expression Sp1, Sp3 Sp4 protein mRNA several Sp-dependent genes including survivin, vascular endothelial factor (VEGF), VEGF receptor 1 (VEGFR1 or Flt-1). also induced apoptosis, arrested at G(2)/M, tumor athymic nude mice bearing...
Abstract Nurr1 is an orphan nuclear receptor and a member of the nerve growth factor I-B subfamily transcription factors with no known endogenous ligand or stimulator. We show, for first time, evidence that expressed in panel 11 human bladder cancer cell lines. A new class methylene-substituted diindolylmethanes (C-DIM) were screened 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane (DIM-C-pPhCl) activated ligand-binding domain Nurr1. Treatment cells Nurr1-active C-DIM resulted decreased...
Abstract 1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes containing p-trifluoromethyl (DIM-C-pPhCF3), p-t-butyl (DIM-C-pPhtBu), and phenyl (DIM-C-pPhC6H5) substituents have been identified as a new class of peroxisome proliferator-activated receptor γ (PPARγ) agonists that exhibit antitumorigenic activity. The PPARγ-active C-DIMs not previously studied against bladder cancer. We investigated the effects on cancer cells in vitro tumors vivo. In this study, compounds inhibited...
1,1-Bis-(3′-indolyl)-1-(<i>p</i>-substitutedphenyl)methanes containing <i>p</i>-trifluoromethyl (DIM-C-pPhCF<sub>3</sub>), <i>p-t</i>-butyl (DIM-C-pPhtBu), and phenyl (DIM-C-pPhC<sub>6</sub>H<sub>5</sub>) substituents decrease survival of HCT-116 colon cancer cells activate peroxisome proliferator-activated receptor (PPAR) γ in this other cell lines. These PPARγ-active compounds had minimal effects on expression cycle proteins did not induce caveolin-1 cells. However, these induced...
Abstract Glycyrrhizin, a pentacyclic triterpene glycoside, is the major phytochemical in licorice. This compound and its hydrolysis product glycyrrhetinic acid have been associated with multiple therapeutic properties of licorice extracts. We investigated effects 2-cyano substituted analogues on their cytotoxicities activity as selective peroxisome proliferator–activated receptor γ (PPARγ) agonists. Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (β-CDODA-Me) methyl...
The non-steroidal anti-inflammatory drug tolfenamic acid (TA) inhibits proliferation of SEG-1 and BIC-1 esophageal cancer cells with half-maximal growth inhibitory concentration values 36 48 μM, respectively. TA also increased Annexin V staining in both cell lines, indicative proapoptotic activity. Treatment for up to 72 h decreased expression specificity protein (Sp) transcription factors Sp1, Sp3 Sp4 this was accompanied by the well-characterized Sp-regulated genes cyclin D1, vascular...
2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and the corresponding methyl (CDDO-Me) imidazole (CDDO-Im) esters induce peroxisome proliferator-activated receptor γ (PPARγ)-dependent transactivation in SW-480 colon cancer cells, these responses were inhibited by small inhibitory RNA for PPARγ. Moreover, a mammalian two-hybrid assay using PPARγ<sub>2</sub>-VP16 fusion plasmid GAL4-coactivator/corepressor chimeras construct (pGAL4) containing five tandem GAL4 response elements, CDDO,...
Nerve growth factor-induced B (NGFI-B) genes are orphan nuclear receptors, and NGFI-Bα (Nur77, TR3) is overexpressed in bladder tumors cancer cells compared with nontumorous tissue. 1,1-Bis(3′-indolyl)-1-(<i>p</i>-methoxyphenyl)-methane (DIM-C-pPhOCH<sub>3</sub>) 1,1-bis(3′-indolyl)-1-(<i>p</i>-phenyl)methane have previously been identified as activators of Nur77, both compounds inhibited induced apoptosis UC-5 KU7 cells. The proapoptotic effects methylene-substituted diindolylmethanes...
Androgen-insensitive DU145 and PC3 human prostate cancer cells express high levels of specificity protein (Sp) transcription factors Sp1, Sp3, Sp4, treatment with methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) inhibited cell growth downregulated Sp4 expression. CDODA-Me (15 mg/kg/d) was a potent inhibitor tumor in mouse xenograft model (PC3 cells) also decreased expression Sp tumors. CDODA-Me-mediated downregulation due to induction the transcriptional repressor ZBTB4,...
Angiopoietin-2 (Ang2), a ligand of the endothelial Tie2 tyrosine kinase, is involved in vascular inflammation and leakage critically ill patients. However, role Ang2 demyelinating central nervous system (CNS) autoimmune diseases unknown. Here, we report that pathogenesis experimental encephalomyelitis (EAE), rodent model multiple sclerosis. expression was induced CNS autoimmunity, transgenic mice overexpressing specifically cells (ECs) developed significantly more severe EAE. In contrast,...
Abstract 1,1-Bis(3′indolyl)-1–(p-substitutedphenyl)methanes containing p-trifluoromethyl (DIM-C-pPhCF3), p-t-butyl (DIM-C-pPhtBu), and p-phenyl (DIM-C-pPhC6H5) groups induce peroxisome proliferator-activated receptor γ (PPARγ)-mediated transactivation in HT-29, HCT-15, RKO, SW480 colon cancer cell lines. Rosiglitazone also induces these lines inhibited growth of HT-29 cells, which express wild-type PPARγ but not HCT-15 mutant (K422Q) PPARγ. In contrast, DIM-C-pPhCF3, DIM-C-pPhtBu,...