Synthesis of a natural chalcone and its prenyl analogs--evaluation of tumor cell growth-inhibitory activities, and effects on cell cycle and apoptosis

Six prenyl (=3-methylbut-2-en-1-yl) chalcones (=1,3-diphenylprop-2-en-1-ones), 2-7, and one natural non-prenylated chalcone, 1, have been synthesized and evaluated for their in vitro growth-inhibitory activity against three human tumor cell lines. A pronounced dose-dependent growth-inhibitory effect was observed for all prenylated derivatives, except for 7. The chalcone possessing one prenyloxy group at C(2'), i.e., 2, was the most active derivative against the three human tumor cell lines (5.9相似文献   

The thermodynamics of interaction between Sephadex and penetrating solutes

1. We have measured the partition coefficients of bovine serum albumin with Sephadex grades G-100, G-150 and G-200, and of a dextran ([unk]_n 19700) and a polyethylene glycol ([unk]_n 8000) with Sephadex G-200. We have also measured the effects of these solutes on the inner volumes of the grades of Sephadex. 2. The results can be described with fair consistency by means of a simple thermodynamic treatment that makes use of the virial coefficients of Sephadex and of the solute, and of a coefficient that expresses their interaction. This coefficient is related to the `exclusion volume' of Sephadex for the solutes. 3. The Sephadex G-200–polyethylene glycol system shows anomalies of behaviour that are ascribed to the occurrence of `incompatible' phase separation within the Sephadex beads.     

Fractionation of a hyaluronic acid preparation in a density gradient. Some properties of the hyaluronic acid

1. Hyaluronic acid was isolated from ox synovial fluid by sedimentation equilibrium in a caesium chloride density gradient (Silpananta, Dunstone & Ogston, 1967). The product was almost free from chondroitin sulphate and from protein. 2. Its composition did not differ significantly from that of the carbohydrate part of the protein-containing material isolated by filtration. Its physicochemical properties and molecular configuration were similar, except for its viscosity, which showed markedly reduced concentration-dependence and shear-dependence. This suggests that the associated protein tends to form links between molecules of hyaluronic acid. 3. The accurate measurement of viscosity at very low velocity gradient, by use of the damping of oscillations in a Couette viscometer, is described. 4. A method is described for measuring, approximately, the thermodynamic non-ideality of a solute from the shape of its schlieren curve at sedimentation equilibrium in a density gradient. 5. A value for the partial specific volume of hyaluronic acid in dilute salt solution was calculated from its isopycnic density in a caesium chloride gradient.     

Fractionation of a hyaluronic acid preparation in a density gradient: The isolation and identification of a chondroitin sulphate

1. Following the suggestion of Nichol, Ogston & Preston (1967) that hyaluronic acid, prepared by filtration from ox synovial fluid, contains a component of high density, such material has been detected and isolated by equilibrium sedimentation in a density gradient of caesium chloride. 2. This material (fraction III) has been characterized as a chondroitin sulphate-protein complex of average molecular weight about 250000. Its amino acid pattern is characteristic of such complexes present in cartilage. It contains a proportion of glucosamine (as well as galactosamine); this is not due to contamination with hyaluronic acid. 3. Preliminary findings on fraction I (low density) and fraction II (intermediate density) suggest that these consist chiefly of protein and hyaluronic acid respectively.     

Bamboo extract reduces interleukin 6 (IL-6) overproduction under lipotoxic conditions through inhibiting the activation of NF-κB and AP-1 pathways

Interleukin 6 (IL-6) is an inflammatory cytokine overexpressed in obese individuals that contributes to the development of diseases such as insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the inhibitory effect of an extract from the bamboo Phyllostachys edulis (BEX) on lipotoxicity-induced over-production of IL-6 in metabolic cell lines. Palmitic acid (PA, 0.4mM) was used to induce lipotoxicity in murine C2C12, 3T3-L1, and Hepa6 cells. Both intra- and extra-cellular protein concentrations of IL-6 were measured in the three cell lines after PA treatment with or without the presence of BEX using cytometric bead assays. IL-6 mRNA levels were quantified using real-time PCR, and nuclear concentrations of c-fos, p50 and p65 proteins were measured using DNA-binding ELISA in 3T3-L1 cells. Lipotoxicity increased IL-6 protein concentration in both cytosol and media collected from myoblast and myotube C2C12, as well as preadipose and adipose 3T3-L1, and the presence of BEX (0.5%, v/v) effectively inhibited this overproduction. IL-6 protein expression in hepatic Hepa6 cells was less affected by lipotoxicity. BEX significantly ameliorated PA-induced upregulation of IL-6 mRNA, which correlated with a reduction in nuclear translocation of p50, p65, and c-fos proteins with the presence of BEX, indicating inhibition of NF-κB and AP-1 activation. In summary, BEX inhibits lipotoxicity-induced IL-6 overproduction in muscle and adipose cell lines through the NF-κB and AP-1 pathways, implicating a potential application of this natural product as a cost-effective anti-inflammation nutraceutical.     

Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes

Monocyte Chemoattractant Protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of obesity- and diabetes-related diseases have increased exponentially during the past two decades. This review attempted to provide a panoramic perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized.     

Synthesis of a Natural Chalcone and Its Prenyl Analogs – Evaluation of Tumor Cell Growth‐Inhibitory Activities,and Effects on Cell Cycle and Apoptosis

Six prenyl (=3‐methylbut‐2‐en‐1‐yl) chalcones (=1,3‐diphenylprop‐2‐en‐1‐ones), 2 – 7 , and one natural non‐prenylated chalcone, 1 , have been synthesized and evaluated for their in vitro growth‐inhibitory activity against three human tumor cell lines. A pronounced dose‐dependent growth‐inhibitory effect was observed for all prenylated derivatives, except for 7 . The chalcone possessing one prenyloxy group at C(2′), i.e., 2 , was the most active derivative against the three human tumor cell lines (5.9<GI₅₀<7.7 μM ). The majority of compounds caused an increase in percentage of apoptotic cells and/or they interfered with cell cycle distribution in the MCF‐7 cell line.     

Organic and inorganic compound variations in haemolymph, epidermal tissue and cuticle over the molt cycle in Scylla serrata (Decapoda)

Analysis of organic and inorganic compounds in haemolymph, epidermal tissue and cuticle, allowed the correlation of their content variation during the molt cycle in Scylla serrata (Decapoda). The extrusion of carbohydrate, chitin, H(2)O- and NaOH-soluble proteins of the epidermal tissue from D2 stage on suggested an early formation of the organic fraction in the new cuticle. The additional secretion of HCl-soluble protein, glycosaminoglycans, calcium, phosphorus and sulfur in D2-D3 stages suggests mineral nucleation shortly before or at ecdysis. This is consistent with the dominant content of proteins and chitin associated with peaks of carbohydrates and GAG-sulfur groups detected in the cuticle immediately after ecdysis. Furthermore, the maximal phosphorus content at this moment suggests calcium, magnesium and manganese phosphate deposits. After an intense accumulation of calcium, chitin and sharp decrease of protein from A to B stages, a constant rate of their deposition in intermolt and dissolution in premolt occurred. The variations concerning proteins, carbohydrates, glycosaminoglycans, calcium, magnesium and sulfur in the haemolymph, before and after ecdysis, suggest a transitory phenomenon for calcium binding and releasing. Other major elements such as, sodium, potassium and chloride may function as osmotic regulators in the haemolymph and in epidermal compartments. The copper profile presented an indicator role for variations of osmolality over the molt cycle.     

The responses of HT22 cells to the blockade of mitochondrial complexes and potential protective effect of selenium supplementation

Mitochondria are the major reactive oxygen species (ROS)--generating sites in mammalian cells. Blockade of complexes in the electron transport chain (ETC) increases the leakage of single electrons to O(2) and therefore increases ROS levels. Complexes I and III have been reported to be the major ROS-generating sites in mitochondria. In this study, using mouse hippocampal HT22 cells as in vitro model, we monitored the change of intracellular ROS level in response to the blockade of ETC at different complex, and measured changes of gene expression of antioxidant enzymes and phase II enzymes, also evaluated potential protective effect of selenium (Se) supplementation to the cells under this oxidative stress. In summary, our results showed that complex I was the major ROS-generating site in HT22 cells. Complex I blockade upregulated the mRNA levels of glutamylcysteine synthetase heavy and light chains, glutathione-S-transferases omega1 and alpha 2, hemoxygenase 1, thioredoxin reductase 1, and selenoprotein H. Unexpectedly, the expression of the enzymes that directly scavenge ROS decreased, including superoxide dismutases 1 and 2, glutathione peroxidase 1, and catalase. Se supplementation increased glutathione levels and glutathione peroxidase activity, indicating a potential protective role in oxidative stress caused by ETC blockade.     

Overexpression of selenoprotein H reduces Ht22 neuronal cell death after UVB irradiation by preventing superoxide formation

Selenoproteins have been shown to exhibit a variety of biological functions, including antioxidant functions, maintaining cellular redox balance, and heavy metal detoxification. UV irradiation-induced damage is partially mediated by increased oxygen radical production. The present study is designed to examine the antioxidative effects of human selenoprotein H (hSelH) after brief period of UVB irradiation on the murine hippocampal neuronal cell line Ht22. Ht22 cells were stably transfected with the hSelH gene or with MSCV empty vector and exposed to UVB irradiation with or without the presence of serum. The results showed that cell viability was significantly higher in hSelH-transfected cells compared to the MSCV vector-transfected cells after 24 h of recovery with or without the presence of serum in the media. Further studies revealed that while the number of superoxide anion (O2*-) positive cells was increased following a 7 mJ/cm(2) of UVB irradiation and 5 h of recovery, overexpression of hSelH significantly reduced superoxide production. These results suggest that hSelH overexpression protects cells from UVB irradiation-induced cell death by reducing the O2*- formation.