The tryptophan metabolites indole, indole-3-acetate, and tryptamine were identified in mouse cecal extracts fecal pellets by mass spectrometry. aryl hydrocarbon receptor (AHR) agonist antagonist activities of these microbiota-derived compounds investigated CaCo-2 intestinal cells as a model for understanding their interactions with colonic tissue, which is highly (Ah)–responsive. Activation Ah-responsive genes demonstrated that indole 3-acetate AHR agonists, whereas was an inhibited TCDD...

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...

Abstract Background Classifications of intraductal papillary mucinous neoplasm (IPMN) remain ambiguous, especially for the mixed type. Factors predicting malignancy unclear. The aim this study was to evaluate usefulness factors in new international consensus guidelines resection branch duct-type (BD)-IPMN and compare them with those previous version. Methods A prospectively collected database patients biopsy-proven BD-IPMN analysed between first second guidelines, particularly as predictors...

Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action aspirin in are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis decreased cell growth salt also inhibited tumor an athymic nude mouse xenograft model. Colon inhibition was accompanied by downregulation Sp1, Sp3 Sp4 proteins expression Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET p65...

Patients with ER-negative breast tumors are among the most difficult to treat and exhibit low survival rates due, in part, metastasis from various distal sites. Aryl hydrocarbon receptor (AHR) ligands show promise as antimetastatic drugs for estrogen (ER)-negative cancer. Triple negative MDA-MB-231 cancer cells were treated eight AHR-active pharmaceuticals including 4-hydroxtamoxifen, flutamide leflunomide, mexiletine, nimodipine, omeprazole, sulindac tranilast, effects of these compounds on...

NR4A1 (Nur77, TR3) is an orphan nuclear receptor that overexpressed in pancreatic cancer and exhibits pro-oncogenic activity. RNA interference of expression Panc-1 cells induced apoptosis subsequent proteomic analysis revealed the induction several markers endoplasmic reticulum stress, including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous (CHOP), activating transcription factor-4 (ATF-4). Treatment with antagonist...

1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methane (C-DIM) compounds exhibit antineoplastic activity in multiple cancer cell lines and the p-hydroxyphenyl analog (DIM-C-pPhOH) inactivates nuclear receptor 4A1 (NR4A1) lung pancreatic lines. Using a series of 14 different p-substituted phenyl C-DIMs, we show that several including DIM-C-pPhOH directly interacted with ligand binding domain NR4A1. Computational-based molecular modeling studies showed high-affinity interactions related within...

Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines animal models. In this study, the eight AHR-active were investigated highly aggressive (Ah)-responsive BT474 MDA-MB-468 breast cancer lines, their effects on AHR protein, CYP1A1 (protein mRNA), CYP1B1 (mRNA), migration determined. 2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin (TCDD)...

Treatment of ErbB2-overexpressing BT474 and MDA-MB-453 breast cancer cells with 1 to 10 μmol/L betulinic acid inhibited cell growth, induced apoptosis, downregulated specificity protein (Sp) transcription factors Sp1, Sp3, Sp4, decreased expression ErbB2. Individual or combined knockdown Sp4 by RNA interference also ErbB2 this response was because repression YY1, an Sp-regulated gene. Betulinic acid-dependent genes due, in part, induction the Sp repressor ZBTB10 downregulation microRNA-27a...

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...

NR4A1 (Nur77, TR3) is overexpressed in pancreatic tumors and activation of TR3 by 1,1-bis(3′-indolyl)-1-( p -methoxyphenyl)methane (DIM-C-pPhOCH 3 ) inhibits cell tumor growth induces apoptosis. Microarray analysis demonstrates that L3.6pL cancer cells DIM-C-pPhOCH genes associated with metabolism, homeostasis, signal transduction, transcription, stress, transport, immune responses, inhibition Among the most highly induced inhibitory proapoptotic including activating transcription factor...

The orphan nuclear receptor NR4A1 exhibits pro-oncogenic activity in cancer cell lines. activates mTOR signaling, regulates genes such as thioredoxin domain containing 5 and isocitrate dehydrogenase 1 that maintain low oxidative stress, coactivates specificity protein (Sp1)-regulated pro-survival growth promoting genes. Transfection of renal carcinoma (RCC) ACHN 786-O cells with oligonucleotides target results a 40–60% decrease proliferation induction apoptosis. Moreover, knockdown RCC...

Overexpression of the nuclear receptor 4A1 (NR4A1) in breast cancer patients is a prognostic factor for decreased survival and increased metastasis, this has been linked to NR4A1-dependent regulation transforming growth β (TGF-β) signaling. Results RNA interference studies demonstrate that basal migration aggressive SKBR3 MDA-MB-231 cells TGF-β independent dependent on β1-integrin gene expression by NR4A1 which can be inhibited antagonists 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane...

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in mammary tumors and breast cancer cell lines. functional activity of this was investigated by RNA interference with oligonucleotides targeted to NR4A1 (siNR4A1) treatment antagonists. Breast cells were treated antagonists or transfected siNR4A. Effects on proliferation apoptosis as well specific genes associated these responses MCF-7, SKBR3, MDA-MB-231 cells, athymic nude mice bearing xenografts. Transfection MDA-MB-231, SKBR3...

Abstract Background Flavonoids exhibit both chemopreventive and chemotherapeutic activity for multiple tumor types, however, their mechanisms of action are not well defined. Based on some functional gene modifying activities as anticancer agents, we hypothesized that kaempferol quercetin were nuclear receptor 4A1 (NR4A1, Nur77) ligands confirmed compounds directly bound NR4A1 with K D values 3.1 0.93 μM, respectively. Methods The determined in direct binding to protein NR4A1-dependent...

Adipocytes secrete adipokines, bioactive molecules crucial for various physiological processes, such as enhancing insulin sensitivity, promoting wound healing, supporting hair growth, and exhibiting anti-aging effects on the skin. With growing global demand sustainable alternative protein sources, insect-derived proteins, particularly from Tenebrio molitor (mealworms), have gained attention due to their high nutritional value functional bioactivities. This study aims explore potential of...