chondroitin and Liver-Neoplasms

Topics: Acetamides; Azo Compounds; Biological Transport, Active; Carcinogens; Carcinoma, Hepatocellular; Cells, Cultured; Chondroitin; Ethionine; Glucose; Glycogen; Glycosaminoglycans; Heparin; Histocytochemistry; Hyaluronic Acid; Liver; Liver Glycogen; Liver Neoplasms; Microscopy, Electron; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Nitrosamines; Polysaccharides; Radiation Effects

The first choice of treatment in Hepatocellular Carcinoma (HCC) is 5-fluorouracil (5-FU). Nitroxoline (NIT), a potent inhibitor of Cathepsin B, impairs tumor progression by decreased extracellular matrix degradation. The objective of the current project was designed to target nanoparticles for co-delivery of 5-FU and NIT in order to enhance the 5-FU cytotoxic effects and reduce the metastatic properties of HepG2 cells.. 5-FU and NIT were loaded in chitosan-chondroitin nanoparticles. To target the CD44 receptors of HepG2 cells, Hyaluronic Acid (HA) was conjugated to the chondroitin by adipic acid dihydrazide and the conjugation was confirmed by FTIR and 1HNMR. After physicochemical characterization and optimization of the processing variables, MTT assay was done on HepG2 and NIH3T3 cell lines to determine the cytotoxic properties of HA targeted nanoparticles. Migration of the cells was studied to compare the co-delivery of the drugs with each drug alone.. The optimized nanoparticles showed the particle size of 244.7±16.3nm, PDI of 0.30±0.03, drug entrapment efficiency of 46.3±5.0% for 5-FU and 75.1±0.9% for NIT. The drug release efficiency up to 8 hours was about 37.6±0.9% for 5-FU and 62.9±0.7% for NIT. The co-delivery of 5-FU and NIT in targeted nanoparticles showed significantly more cytotoxicity than the mixture of the two free drugs, non-targeted nanoparticles or each drug alone and reduced the IC50 value of 5-FU from 3.31±0.65μg/ml to 0.17±0.03μg/ml and the migration of HepG2 cells was also reduced to five-fold.. Co-delivery of 5-FU and NIT by HA targeted chitosan-chondroitin nanoparticles may be promising in HCC.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cathepsin B; Chitosan; Chondroitin; Drug Liberation; Drug Therapy, Combination; Fluorouracil; Hep G2 Cells; Humans; Hyaluronic Acid; Liver Neoplasms; Mice; Molecular Targeted Therapy; Nanocapsules; NIH 3T3 Cells; Nitroquinolines; Protease Inhibitors

Liver cancer is a serious liver disease in which hepatoma cells and activated hepatic stellate cells (HSCs) overproduce extracellular matrix (ECM), which involves the Golgi apparatus. Here chondroitin-modified lipid nanoparticles (CSNs) were prepared and loaded with doxorubicin (DOX) and retinoic acid (RA) using a thin-film hydration-high pressure homogenization method. The resulting DOX + RA-CSNs were efficiently taken up by SMMC-7721 hepatoma cells and HSCs in culture, where they accumulated in the Golgi apparatus and destroyed it, inhibiting ECM production. Injecting DOX + RA-CSNs into mice with primary liver cancer or H22 allografts led to significantly higher tumor penetration by DOX and RA, greater antitumor efficacy, and lower DOX-related toxicity than injecting a solution of the two drugs. Immunofluorescence and immunohistochemistry of liver tissues showed that DOX + RA-CSNs dramatically reduced expression of the ECM components. These results suggest that CSNs show potential for targeting drugs to the Golgi apparatus of liver cancer cells and potentially other types of tumors.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Chondroitin; Doxorubicin; Drug Delivery Systems; Extracellular Matrix; Golgi Apparatus; Humans; Lipids; Liver Neoplasms; Male; Mice; Nanoparticles; Tretinoin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Glycosaminoglycan-modified proteoglycans play important roles in many cell activities, including cell differentiation and stem cell development. Tumor sphere formation ability is one of properties in cancer stem cells (CSCs). The correlation between CSC markers and proteoglycan remains to be clarified. Upon hepatoma sphere formation, expression of CSC markers CD13, CD90, CD133, and CD44, as well the syndecan family protein syndecan-1 (SDC1), increased as analyzed by PCR. Further examination by suppression of CD13 expression showed downregulation of SDC1 and CD44 gene expression, whereas suppression of SDC1 gene expression downregulated CD13 and CD44 gene expression. Suppression of SDC1 gene expression also suppressed sphere development, as analyzed by a novel sphereocrit assay to quantify the level of sphere formation. The heparin disaccharide components, but not those of chondroitin disaccharide, changed with hepatoma sphere development, revealing the increased levels of

Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; CD13 Antigens; Cell Line, Tumor; Chondroitin; Disaccharides; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Heparin; Humans; Hyaluronan Receptors; Liver Neoplasms; Neoplastic Stem Cells; Polymerase Chain Reaction; Proteoglycans; Spheroids, Cellular; Syndecan-1; Up-Regulation

The incorporation of 35S into the sulfated mucopolysaccharides from hepatoma, normal and embryonic liver cells has been studied by means of anion exchange chromatography of the isolated mucopolysaccharide. Comparatively to liver cells, while showing a higher labeling of low sulfated mucopolysaccharides the hepatoma cells incorporate much less 35S into the heparin fraction.

Topics: Animals; Ascitic Fluid; Carcinoma, Hepatocellular; Chondroitin; Female; Glycosaminoglycans; Heparin; Heparitin Sulfate; Liver; Liver Neoplasms; Pregnancy; Rats; Sulfates

A method is proposed for the analysis of glycosaminoglycans that were isolated from human liver, combining cellulose acetate electrophoresis and enzymatic digestion with mucopolysaccharidases. The major constituent of glycossaminoglycans in the healthy liver is heparin sulfate and/or heparin (about 65%), with approximately equal quantities of dermatan sulfate and hyalauronic acid (about 13.5 and 13%, respectively) and a small amount of chondroitin sulfate. These components, especially chondroitin sulfate and hyaluronic acid, are markedly increased in hepatic carcinomas.

Topics: Adenoma, Bile Duct; Carcinoma, Hepatocellular; Chondroitin; Dermatan Sulfate; Electrophoresis; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Hyaluronic Acid; Hydrolysis; Liver; Liver Neoplasms

Beta-Xylosides stimulate 2- to 6-fold the synthesis of glycosaminoglycans by three types of nonconnective tissue cells (RG-C6, NB41A, and rat hepatoma cells, and normal and simian virus 40 (SV40)-transformed normal human skin fibroblasts. The effect, which is specific for the anomeric linkage and the glycone, is observed in the presence and absence of puromycin. Beta-Xylosides may substitute for xylosylated core protein as initiators of synthesis of chondroitin sulfate chains. No stimulation of synthesis of heparan sulfate was observed. With the use of a fluorogenic xyloside, 4-methylumbelliferyl-beta-D-xyloside, it was demonstrated that the free chondroitin sulfate chains secreted into the medium bear the xyloside at the reducing end, and have an average molecular weight of 16,500.

Topics: Animals; Carcinoma, Hepatocellular; Cells, Cultured; Chondroitin; Chromatography, Gel; Dermatan Sulfate; Fibroblasts; Galactose; Glycosaminoglycans; Glycosides; Heparitin Sulfate; Humans; Hyaluronic Acid; Hymecromone; Liver Neoplasms; Mice; Neuroblastoma; Neuroglia; Nitrophenols; Rats; Simian virus 40; Skin; Spectrometry, Fluorescence; Sulfur Radioisotopes; Sulfuric Acids; Tritium; Xylose

Topics: Animals; Carcinoma, Hepatocellular; Chondroitin; Chromatography, Ion Exchange; Electrophoresis; Glucosamine; Glycosaminoglycans; Heparin; Hexosamines; Hexoses; Hyaluronic Acid; Liver Neoplasms; Methylcholanthrene; Neoplasm Transplantation; Neoplasms, Experimental; Proteins; Rats; Sarcoma, Experimental; Spectrophotometry, Infrared; Sulfates; Transplantation, Homologous; Uronic Acids

Previous studies have shown that D-xylose partially overcomes the puromycin inhibition of chondroitin sulfate synthesis in cultured chick embryo chondrocytes. Likewise, D-xylose stimulates chondroitin sulfate synthesis by limb bud mesenchyme cells previously treated with BrdU or limb bud cartilage cells treated with puromycin. The studies reported here show that p-nitrophenyl-beta-D-xylopyranoside and 4-methyl-umbelliferyl-beta-D-xylopyranoside cause a much greater stimulation than does D-xylose and are active at much lower concentrations. In contrast to D-xylose, the xylosides strikingly stimulate chondroitin sulfate synthesis in predifferentiated mesenchyme cells. The xylosides stimulate synthesis of chondroitin sulfate by rat glial cell tumor cells (RC-6), a mouse neuroblastoma (C1300, NB41A), and two strains of cultured rat hepatoma cells (HTC, H(4)). These results indicate that certain types of nonconnective tissue cells contain the enzymic machinery for synthesis of chondroitin sulfate which is normally not utilized because of limited synthesis of core protein and/or xylosyltransferase. The beta-xylosides may be used as a probe of the capacity of various cell types to synthesize sulfated glycosaminoglycans.

Topics: Animals; Bromodeoxyuridine; Carcinoma, Hepatocellular; Cartilage; Cell Line; Cells, Cultured; Chick Embryo; Chondroitin; Coumarins; Glioma; Glycosaminoglycans; Glycosides; Liver Neoplasms; Mice; Neuroblastoma; Puromycin; Rats; Stimulation, Chemical; Xylose

The metabolism of acid mucopolysaccharides in Novikoff hepatoma and in hepatoma BW7756 was studied using the precursors -35S-sulfate, -H-glucosamine and -14C-galactosamine. There is an active formation of sulfated mucopolysaccharides at the mitochondria and cell membrane level. Hepatoma cells synthesize heparin to a lower rate than liver cells. In ascitic as well as in solid tumors there is a considerable accumulation of hyaluronic acid which does not seem to be elicited by the tumor cells but by the surrounding tissues. The possible implication of the low heparin production in the cell membrane characteristics is discussed.

Topics: Animals; Ascitic Fluid; Carcinoma, Hepatocellular; Cell Membrane; Chondroitin; Galactosamine; Glucosamine; Glycosaminoglycans; Heparin; Hexosamines; Hyaluronic Acid; Liver; Liver Neoplasms; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Neoplasms, Experimental; Rats; Sulfates; Uronic Acids

Topics: Agglutination; Agglutination Tests; Animals; Binding Sites; Carcinoma, Hepatocellular; Cetylpyridinium; Chondroitin; Chromatography; Coloring Agents; Electrophoresis, Polyacrylamide Gel; Glucose; Glycoproteins; Glycosaminoglycans; Hyaluronoglucosaminidase; Lanthanum; Liver Neoplasms; Mice; Microscopy, Electron; Neoplasms, Experimental; Papain; Rats; Ruthenium; Staining and Labeling; Trypsin

Topics: Animals; Carcinoma, Hepatocellular; Cell Line; Chondroitin; Chromatography; Electrophoresis; Glycosaminoglycans; Hyaluronic Acid; In Vitro Techniques; Liver Neoplasms; Male; Neoplasms, Experimental; Rats; Sarcoma, Yoshida

Topics: Animals; Carcinoma, Hepatocellular; Cell Line; Cell Membrane; Chondroitin; Chromatography, Paper; Culture Techniques; Electrophoresis; Glycosaminoglycans; Liver Neoplasms; Lyases; Membrane Potentials; Neoplasms, Experimental; Neuraminic Acids; Neuraminidase; Rats; Sulfates; Sulfur Isotopes

Topics: Amnion; Cell Line; Cell-Free System; Chondroitin; DNA, Neoplasm; Heparin; Humans; Hyaluronic Acid; Liver Neoplasms; Neoplasm Metastasis; Polysaccharides; Sulfates; Thymidine; Tritium

Topics: Animals; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Chondroitin; In Vitro Techniques; Liver Neoplasms; Mice; Neoplasms, Experimental; Rats