Cleogynol, a novel dammarane triterpenoid from Cleome gynandra

Chemical examination of Cleome gynandra (whole plant excluding seeds) led to the isolation and identification of a novel (20S,24S)-epoxy-19,25-dihydroxydammarane-3-one hemiketal. The structure of the new compound, designated cleogynol, was determined using spectral and chemical methods

Downregulation of Wnt/β-catenin self-renewal pathway in cervical cancer cells by polyphenolic compounds

673-680Cervical cancer is the second most common cancer in woman of developing countries. Wnt/β-catenin self-renewal pathway is important for cervical cancer initiation and progression. Plumbagin, Pongapin and Karanjin are three plant polyphenols with known anticancer activities. Thus, this study aims to analyze the effects of these compounds on Wnt/β-catenin pathway in cervical cancer cells (HeLa), due to their high sensitivity in this cell line. The compounds significantly downregulated the co-receptor LRP6 (low density lipoprotein receptor related protein 6) expression (mRNA/ protein) in HeLa cells without any change in the expression of receptor FZD7 (Frizzled class receptor 7). The low membrane expression of LRP6 seen in the immunocytochemical analysis might be due to upregulation of its antagonist Dickkopf 1 (DKK1) protein. The compounds could also increase the expression ofFZD7 antagonists, SFRP1/2 (mRNA/protein) in HeLa cells. The upregulation of SFRPs (secreted frizzled-related protein) was due to their promoter hypomethylation through downregulation of DNMT1 (DNA methyltransferase 1) protein by the compounds. As a result, there was downregulation of effector protein β-catenin and activated phospho-β-catenin (Y654) of the pathway in HeLa cells by these compounds. Thus, the polyphenols differentially inhibit the Wnt/β-catenin pathway to restrict cervical cancer proliferation, suggesting their therapeutic importance

PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas

Immune evasion and metabolic reprogramming are hallmarks of cancer progression often associated with a poor prognosis and frequently present significant challenges for cancer therapies. Recent studies have highlighted the dynamic interaction between immunosuppression and the dysregulation of energy metabolism in modulating the tumor microenvironment to promote cancer aggressiveness. However, a pan-cancer association among these two hallmarks, and a potent common driver for them—epithelial-mesenchymal transition (EMT)—remains to be done. This meta-analysis across 184 publicly available transcriptomic datasets as well as The Cancer Genome Atlas (TCGA) data reveals that an enhanced PD-L1 activity signature along with other immune checkpoint markers correlate positively with a partial EMT and an elevated glycolysis signature but a reduced OXPHOS signature in many carcinomas. These trends were also recapitulated in single-cell, RNA-seq, time-course EMT induction data across cell lines. Furthermore, across multiple cancer types, concurrent enrichment of glycolysis and PD-L1 results in worse outcomes in terms of overall survival as compared to enrichment for only PD-L1 activity or expression. These results highlight potential functional synergy among these interconnected axes of cellular plasticity in enabling metastasis and multi-drug resistance in cancer

Liquid Crystalline Aryltriazene-1-Oxides with Two Ester Units: Synthesis, Characterisation, Structure and Thermal Properties

A new series of mesogenic triazene-1-oxides, C6H5-N(O)=N-NH-C6H4-C(O)-O- C6H4-O-(O)C-C6H4-OR (1, R=n-alkyl group from CH3 to C14H29), was designed and synthesised. All members of this new series were characterised on the basis of spectral and analytical data. The thermotropic liquid crystalline behaviour of the compounds was observed over a wide temperature range using optical microscopy. The mesophase structure was confirmed by a small-angle X-ray diffraction study of a representative member (1k). The molecular structure of compound 1i was determined using the single crystal X-ray diffraction method as a representative case. Dimer formation in the solid state occurs due to intermolecular N-H...O and C-H...O interactions. Intermolecular C-H...&pi interactions were also detected in 1i. The intermolecular hydrogen bonding and intermolecular C-H...p interactions arrange the phenyl triazene-1-oxide fragments of the molecules in layers within the molecular assembly

Structure of Liquid Crystalline 1-Phenyl-3-{4-[4-(4-Octyloxybenzoyloxy) Phenyloxycarbonyl]phenyl}triazene-1-Oxide At Low Temperature

The molecular structure of 1-phenyl-3-{4-[4-(4-octyloxybenzoyloxy)- phenyloxycarbonyl]phenyl}triazene-1-oxide, a member of newly developed liquid crystalline homologous series, has been investigated by crystal X-ray crystallography at low temperature (100K). The title compound crystallizes in the triclinic crystal class in the space group P[image omitted] with cell parameters a=5.766(5), b=12.151(10), c=21.751(17), =79.089(13), =88.646(14), =84.278(14), V=1489(2)3 for Z=2. It establishes the N-oxide form of the triazene-1-oxide moiety. The overall molecule is not planar, the dihedral angles between pairs of adjacent benzene rings are 14.00 (10), 52.36 (07), and 50.57 (07). Intramolecular N-HO hydrogen-bonding is present within the triazene-1-oxide moiety of the title compound. The compound forms inversion dimer via an intermolecular N-HO and an intermolecular C-HO links. The dimers are then linked into chains in a parallel fashion by C-HO hydrogen bonds. The crystal packing is further stabilized by C-H interactions

Quantifying the Patterns of Metabolic Plasticity and Heterogeneity along the Epithelial–Hybrid–Mesenchymal Spectrum in Cancer

Cancer metastasis is the leading cause of cancer-related mortality and the process of the epithelial-to-mesenchymal transition (EMT) is crucial for cancer metastasis. Both partial and complete EMT have been reported to influence the metabolic plasticity of cancer cells in terms of switching among the oxidative phosphorylation, fatty acid oxidation and glycolysis pathways. However, a comprehensive analysis of these major metabolic pathways and their associations with EMT across different cancers is lacking. Here, we analyse more than 180 cancer cell datasets and show the diverse associations of these metabolic pathways with the EMT status of cancer cells. Our bulk data analysis shows that EMT generally positively correlates with glycolysis but negatively with oxidative phosphorylation and fatty acid metabolism. These correlations are also consistent at the level of their molecular master regulators, namely AMPK and HIF1α. Yet, these associations are shown to not be universal. The analysis of single-cell data for EMT induction shows dynamic changes along the different axes of metabolic pathways, consistent with general trends seen in bulk samples. Further, assessing the association of EMT and metabolic activity with patient survival shows that a higher extent of EMT and glycolysis predicts a worse prognosis in many cancers. Together, our results reveal the underlying patterns of metabolic plasticity and heterogeneity as cancer cells traverse through the epithelial–hybrid–mesenchymal spectrum of states

Acute toxicity test of a natural iron chelator and an antioxidant, extracted from <i>Triticum aestivum</i> Linn. (wheat grass)

<div><p><i>Triticum aestivum</i> (wheat grass) is widely used in traditional medicine to treat various diseases. Previously the purified compounds and crude extract of <i>T. aestivum</i> were established to have iron chelation potency and antioxidant activity. So it is necessary to evaluate the toxic properties of any compound isolated from plant extract to prevent any untoward side effects. The aim of this study was to determine the acute oral toxicity level of our purified compounds, i.e. <i>mugineic acids and methylpheophorbide a</i>., and crude extract of <i>T. aestivum,</i> on Swiss albino mice at dosage of 2000 mg/kg for a period of 14 days using the organisation for economic co-operation and development guidelines 423. There was no mortality. No change in behavioural pattern, clinical signs, body weight and blood biochemistry profile were observed. Kidney and liver showed normal histo-pathological architecture. Hence, the oral administration of <i>compounds and extract of T. aestivum</i> did not produce any significant toxic effect on mice. Thus we may conclude that the extract can be utilised for pharmaceutical formulations as iron chelator and antioxidant agent for various diseases.</p></div

Antioxidative and anticarcinogenic activities of methylpheophorbide a, isolated from wheat grass (<i>Triticum aestivum</i> Linn.)

<div><p>Methylphophorbide a (MPa) has been isolated from the ethanol extract of the wheat grass plant. Its antioxidative efficacy is evaluated by hydroxyl radical scavenging activities and reducing capacity which are significantly up regulated in comparison with aqueous extract of the plant. The compound shows iron-binding capacity where the Fe²⁺ binds with MPa by two types of binding patterns with dissociation constants 157.17 and 27.89. It has antioxidative and cytotoxic effects on HeLa and Hep G2 cells. The cancerous cell survivability decreases with increasing concentration of MPa. These findings have provided evidence for the traditional use of the wheat grass plant in the treatment of cancers, oxidative stress and iron overloaded disorders.</p></div