Comparative Analysis of Polyphenolic Compounds in Different Species: Influence of Genotypes and Harvesting Year.

Amaranth is a nutritionally valuable crop, as it contains phenolic acids and flavonoids, yielding diverse plant secondary metabolites (PSMs) like phytosterol, tocopherols, and carotenoids. This study explored the variations in the contents of seventeen polyphenolic compounds within the leaves of one hundred twenty accessions representing nine species. The investigation entailed the analysis of phenolic content across nine species, specifically , , , , , , , , and , utilizing ultra performance liquid chromatography with photodiode array detection (UPLC-PDA).

Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation.

Kinetin riboside is a naturally produced cytokinin that displays strong antiproliferative activity in various human cancer cells. However, the mechanism of chemoprevention in colorectal cancer cells has not been elucidated. We used a cell-based reporter system to identify kinetin riboside as an antagonist of the Wnt/β-catenin pathway, which is aberrantly upregulated in colorectal cancer.

Metabolome-Wide Reprogramming Modulated by Wnt/β-Catenin Signaling Pathway.

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process.

Lucidin 3-methyl ether from Rubia philippinensis suppresses the proliferation of multiple myeloma cells through the promotion of β-catenin degradation.

Background: Constitutive accumulation of β-catenin has been frequently observed in multiple myeloma. Extracts from genus Rubia plants exhibit cytotoxic activity against several types of cancer cells; however, little is known about their chemopreventive mechanisms and bioactive metabolites.

Purpose: Purpose: The study aimed to identify the underlying antiproliferative mechanisms of Rubia philippinensis extract in multiple myeloma cells and the major active metabolites responsible for cytotoxic activity of R.

Root Bark of L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/β-Catenin Pathway.

The root bark of L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites.

Synthesis and Application of Silica-Coated Quantum Dots in Biomedicine.

Quantum dots (QDs) are semiconductor nanoparticles with outstanding optoelectronic properties. More specifically, QDs are highly bright and exhibit wide absorption spectra, narrow light bands, and excellent photovoltaic stability, which make them useful in bioscience and medicine, particularly for sensing, optical imaging, cell separation, and diagnosis. In general, QDs are stabilized using a hydrophobic ligand during synthesis, and thus their hydrophobic surfaces must undergo hydrophilic modification if the QDs are to be used in bioapplications.

Absolute oral and subcutaneous bioavailability of ortho-topolin riboside in mice.

Among essential phytohormones playing a pivotal role in regulating growth and development, ortho-topolin riboside (oTR) exerts the most substantial anti-tumor potency in various cancer cell lines. This study was designed to establish a quantitative determination method for oTR in mouse plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), to validate the analytical method including stability, and to characterise its pharmacokinetic behaviour in mice. After simple protein precipitation with acetonitrile including kinetin riboside (internal standard), oTR was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (3:7 v/v, including 0.

Ilimaquinone inhibits neovascular age-related macular degeneration through modulation of Wnt/β-catenin and p53 pathways.

Neovascular age-related macular degeneration (nAMD) is a common cause of irreversible vision loss in the elderly. Anti-vascular endothelial growth factor has been effective in treating pathological ocular neovascularization, but it has limitations including the need for repeated intraocular injections for the maintenance of therapeutic effects in most patients and poor or non-response to this agent in some patients. in vitro cellular studies were conducted using retinal pigment epithelial cell lines (ARPE-19 and hTERT-RPE1), human umbilical vein endothelial cells (HUVECs), and human umbilical vein smooth muscle cells (HUVSMCs).

Cytotoxic Activity of Aplykurodin A Isolated From against -Mutated Hepatocellular Carcinoma Cells by Promoting Oncogenic β-Catenin Degradation.

Dysregulation of the Wnt/β-catenin signaling pathway is involved in the development of human hepatocellular carcinoma and has thus emerged as a therapeutic target for this malignant tumor. In this study, we employed sensitive cell-based assays to identify aplykurodin A isolated from as an antagonist of Wnt/β-catenin signaling. Aplykurodin A inhibited β-catenin responsive transcription, which was stimulated by a Wnt3a-conditioned medium or a glycogen synthase kinase 3β inhibitor by accelerating intracellular β-catenin degradation.

Cytotoxic activity of broussochalcone a against colon and liver cancer cells by promoting destruction complex-independent β-catenin degradation.

Aberrant activation of β-catenin-response transcription (CRT) is a well-recognized characteristic of colorectal and liver cancers and thus a potential therapeutic target for these malignancies. Broussonetia papyrifera (paper mulberry) has been used as a herbal medicine to treat various diseases. Using a sensitive cell-based screening system, we identified broussochalcone A (BCA), a prenylated chalcone isolated from Broussonetia papyrifera, as an antagonist of CRT.

Longan fruit increase bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation.

Background: The receptor activator of nuclear factor-kappa B ligand (RANKL)-induced nuclear factor-kappa B (NF-κB) signaling pathway plays essential roles in osteoclast differentiation and may serve as an attractive target for the development of therapeutics for osteoporosis.

Purpose: This study aimed to identify plant extracts that attenuated RANKL-induced NF-κB signaling pathway and examine their anti-osteoporotic effects in animal model systems.

Methods: Osteoclast differentiation was determined by western blot analysis, RT-PCR, and tartrate-resistant acid phosphatase (TRAP) assay.

CGK062, a small chemical molecule, inhibits cancer upregulated gene 2‑induced oncogenesis through NEK2 and β‑catenin.

The mechanisms through which cancer‑upregulated gene 2 (CUG2), a novel oncogene, affects Wnt/β‑catenin signaling, essential for tumorigenesis, are unclear. In this study, we aimed to elucidate some of these mechanisms in A549 lung cancer cells. Under the overexpression of CUG2, the protein levels and activity of β‑catenin were evaluated by western blot analysis and luciferase assay.

Protopine isolated from Nandina domestica induces apoptosis and autophagy in colon cancer cells by stabilizing p53.

The tumor suppressor p53 plays essential roles in cellular protection mechanisms against a variety of stress stimuli and its activation induces apoptosis or autophagy in certain cancer cells. Here, we identified protopine, an isoquinoline alkaloid isolated from Nandina domestica, as an activator of the p53 pathway from cell-based natural compound screening based on p53-responsive transcription. Protopine increased the p53-mediated transcriptional activity and promoted p53 phosphorylation at the Ser15 residue, resulting in stabilization of p53 protein.

Stereo-Selective Pharmacokinetics of Ilimaquinone Epimers Extracted from a Marine Sponge in Rats.

An ilimquinone (IQ) mixture isolated from , consisting of IQ and epi-ilimaquinone (epi-IQ), exerts anti-HIV, anti-microbial, anti-inflammatory, and anti-cancer effects. An HPLC-MS/MS method was developed for simultaneous determination of the two epimers in rat plasma, separating them using a biphenyl column. Ascorbic acid is added during the sample preparation to ensure the stability of both isomers.

HPLC-MS/MS analysis of ilimaquinone and its application in a pharmacokinetic study in rats.

Ilimaquinone, a metabolite isolated from the marine sponge Hippiospongia metachromia, has antimicrobial, cytotoxic, anti-HIV, anti-inflammatory, and anti-cancer activities. A new quantitative analytical method for determination of ilimaquinone in rat plasma using HPLC-MS/MS was developed and validated. Ascorbic acid was added to ensure the stability of ilimaquinone in plasma.

CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of AXIN1 gene expression.

Axin1, a concentration-limiting component of the β-catenin destruction complex, negatively regulates the Wnt/β-catenin pathway. Axin1 concentration is reported to be regulated by proteasomal degradation; however, its transcriptional regulation has not yet been reported. Here, we demonstrated that CCAAT/enhancer-binding protein-β (C/EBP-β) activates axis inhibition protein 1 (AXIN1) gene expression, thereby attenuating Wnt/β-catenin signaling.

Sesterterpenoid and Steroid Metabolites from a Deep-Water Alaska Sponge Inhibit Wnt/β-Catenin Signaling in Colon Cancer Cells.

The Wnt/β-catenin signaling pathway is known to play critical roles in a wide range of cellular processes: cell proliferation, differentiation, migration and embryonic development. Importantly, dysregulation of this pathway is tightly associated with pathogenesis in most human cancers. Therefore, the Wnt/β-catenin pathway has emerged as a promising target in anticancer drug screening programs.

Anti-proliferative activity of CGK012 against multiple myeloma cells via Wnt/β-catenin signaling attenuation.

The aberrant activation of Wnt/β-catenin signaling is involved in the development of multiple myeloma; thus, this signaling pathway is a potential target for the development of therapeutics for this malignancy. Here, we performed cell-based chemical screening and found that CGK012, a pyranocoumarin compound, suppressed the Wnt3a-CM-mediated activation of β-catenin response transcription. CGK012 induced β-catenin phosphorylation at Ser33/Ser37/Thr41, leading to proteasomal degradation and reducing the level of intracellular β-catenin.

LKY-047: First Selective Inhibitor of Cytochrome P450 2J2.

Highly selective cytochrome P450 CYP2J2 (CYP2J2) inhibitors suitable for reaction phenotyping are currently not available. (7)-(+)-(4-Nitro-phenyl)-acrylic acid, 8,8-dimethyl-2-oxo-6,7-dihydro--pyrano[3,2-g]chromen-7-yl-ester (LKY-047), a decursin derivative, was synthesized, and its inhibitor potencies toward CYP2J2 as well as other cytochrome P450 (P450) enzymes in human liver microsomes (HLM) were evaluated. LKY-047 was demonstrated to be a strong competitive inhibitor of CYP2J2-mediated astemizole -demethylase and terfenadine hydroxylase activity, with values of 0.

Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.

Aberrant up-regulation of Wnt/β-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/β-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels.

Smenospongidine suppresses the proliferation of multiple myeloma cells by promoting CCAAT/enhancer-binding protein homologous protein-mediated β-catenin degradation.

Abnormal up-regulation of β-catenin expression is associated with the development and progression of multiple myeloma and is thus a potential therapeutic target. Here, we screened cell-based natural compounds and identified smenospongidine, a metabolite isolated from a marine sponge, as an antagonist of the Wnt/β-catenin signaling pathway. Smenospongidine promoted the degradation of intracellular β-catenin that accumulated via Wnt3a or 6-bromoindirubin-3'-oxime, an inhibitor of glycogen synthase kinase-3β.

SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells.

Metastatic prostate cancer is the leading cause of morbidity and mortality in men. In this study, we found that expression level of SFMBT2 is altered during prostate cancer progression and has been associated with the migration and invasion of prostate cancer cells. The expression level of SFMBT2 is high in poorly metastatic prostate cancer cells compared to highly metastatic prostate cancer cells.

Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-catenin pathway.

We synthesized (+)-decursin derivatives substituted with cinnamoyl- and phenyl propionyl groups originating from (+)-CGK062 and screened them using a cell-based assay to detect relative luciferase reporter activity. Of this series, compound 8b, in which a 3-acetoxy cinnamoyl group was introduced, most potently inhibited (97.0%) the Wnt/β-catenin pathway.

Hepatitis C virus core protein enhances hepatocellular carcinoma cells to be susceptible to oncolytic vesicular stomatitis virus through down-regulation of HDAC4.

Since hepatitis C virus (HCV) core protein is known to possess potential oncogenic activity, we explored whether oncolytic vesicular stomatitis virus (VSV) could efficiently induce cytolysis in hepatocellular carcinoma cells stably expressing HCV core protein (Hep3B-Core). We found that Hep3B-Core cells were more susceptible to VSV as compared to control (Hep3B-Vec) cells owing to core-mediated inactivation of STAT1 and STAT2 proteins. Core expression induced lower phosphorylation levels of type I IFN signaling proteins such as Tyk2 and Jak1, and a reduced response to exogenous IFN-α, which resulted in susceptibility to VSV.