Study On The Preparation And Antitumor Activities Of Dervivatives Of Glucosamine And Chito-oligosaccharide

The preparation and antitumor activities of derivatives of glucosamine and chito-oligosaccharide were reported herein. The growth inhibitory effects of D-glucosamine hydrochloride, chito-oligosaccharide, N-acetyl glucosamine, glucosamine and arginine on human hepatoma SMMC-7721 cells in vitro were investigated. The results indicated that treatment with D-glucosamine hydrochloride and D-glucosamine resulted in a concentration-dependent reduction in cell growth as measured by MTT assay, which was accompanied by a marked increase in the proportion of S cells as analysed by flow cytometry. Compared with the control group, there was no significant difference of various concentrations of chito-oligosaccharide, N-acetyl glucosamine and arginine. D-glucosamine hydrochloride exhibited inhibition effect against Sarcoma 180 in mice, and it could enhance the weights of thymus and spleen. In addition, it could promote lymphocyte transformation.On the basis of study as described above, a new caboxymethyl glucosamine was prepared in alkaline ethanol, the caboxymethyl degree of which was 97.45%. Then a new amino sugar compound, glucosamine-arginine was synthesized, and its structure was studied by IR spectroscopy, ultraviolet scanning, melting point etc. The growth inhibitory effect of glucosamine-arginine on SMMC-7721 was studied. It could lead to a concentration-dependent reduction in cell growth, and the inhibition ratio of it was higher than that of D-glucosamine hydrochloride at the same concentration. It was found that glucosamine-arginine could induce apoptosis in SMMC-7721 cells as assayed qualitatively by DNA agarose gel electrophoresis, flow cytometry, fluoroscopy and transmission electron microscope.A new proteoglycan PG1 was first isolated from a marine mollusk, Ruditapes philippinarum. It contained 70.09% polysaccharide and 15.4% protein and themolecular weight was about 20kDa according to SDS-PAGE. The effects of PG1 on human hepatoma SMMC-7721 cells and human hepatocyte HL-7702 cells in vitro were investigated by MTT assay. PGl was largely innocuous towards human hepatocyte when tested in the same concentrations shown to be cytotoxic towards human hepatoma cells. In vivo experiments, PGl demonstrated the inhibition effect on the transplanted tumor of Sarcoma 180 with the dosage of 125~500mg/kg. It could enhance the weight of spleen and promote lymphocyte transformation. It is therefore postulated that the antitumor effect of PGl from Ruditapes philippinarum is probably host-mediated and cytocidal.