The Investigation Of The Anti-tumor Effects And Mechanisms Of Pearsonothria Graeffei Saponins

Sea cucumbers saponins, one of the most important bioactive compositions of sea cucumber body well, are proved to have various biological activities, especially the anti-tumor activities. There are differences in the saponins contents between different species of sea cucumbers, based on the differences in living environment and food-intake. In this study, the effects and mechanisms of Pearsonothria graeffei saponins on anti-tumor, anti-metastasis and anti-angiogenesis were determined. The relationship between structure and activities was campared. These may provide support to the application of Pearsonothria graeffei.The investigation of the anti-oxidation and anti-tumor effects of Pearsonothria graeffei saponins in S180 tumor bearing mice was conducted through detecting the anti-tumor rate, the contents of GSH, the activities of GSH-PX and GST in serum and liver. The results showed that Pearsonothria graeffei saponins could inhibit the growth of S180 tumor, and increase the content of GSH (P<0.05), promote the activities of GSH-PX (P<0.05) and GST (P<0.05) in serum and liver. It can be concluded that Pearsonothria graeffei saponins could promote the activities of endogenous anti-oxidation enzymes and increase the content of anti-oxidation substance, which attribute to the effect of anti-tumor.The investigation of the anti-tumor activities and mechanisms of Pearsonothria graeffei triterpene glycosides holothurin A1(HA) and 24-dehydroechinoside A (DA)was conducted. The MTT assay was used to determine the anti-proliferation ability. The results suggested that HA and DA could inhibit the proliferation activity of HepG2, B16, Caco-2, Hela, P388 and S180 cells(P<0.01) and the effects on HepG2 cells was most notable. The LDH assay was used to determine the LDH content in the medium treated after HA and DA. The ability of HA and DA of inducing HepG2 cell apoptosis was observed by inverted microscope and fluorescence microscope and examined by the flow cytometry. The results showed that HA and DA could stop the cells in the G0/G1 phase and induce the apoptosis of HepG2 cells. It is suggested that the HA and DA have cytotoxicity on abroad tumor cells and could inhibit the growth of HepG2 cells via inducing cell apoptosis and G0/G1 cell cycle arrested.The investigation of the anti-tumor metastasis effects and mechanisms of HA and DA were conducted. The results showed that HA and DA could inhabit ability of migration (P<0.05), adhesion (P<0.01) and invasion (P<0.01) of HepG2 cells and reduce the expression of matrix metalloproteinase-9 (MMP-9) and promote the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). It is suggested that HA and DA could inhibit the expression of the enzyme of invasion, decrease the adhesion, prevent the migration and thus prevent the metastasis of tumor cell.The investigation of the anti-angiogenesis effects and mechanisms of HA and DA were conducted. The results showed that HA and DA could induce the apoptosis of ECV304 cells, inhibit the tube formation in vitro, decrease the blood vessel growth on the chicken chorioallantoic membrane and reduce the expression of Vascular Endothelial Growth Factor (VEGF). It is suggested that HA and DA could induce the apoptosis of endothelial cell and decrease the expression of angiogenic growth factor and thus prevent the tumor angiogenesis.The relationship between structure and activity was conducted. The results showed that the effect of DA was better than HA. HA has a hydroxy substituted on C-22, DA has a carbon carbon bonds on 24(25). The results showed that the hydroxy substituted on C-22 would decrease the anti-tumor and anti-metastasis activity of triterpene glycosides. The carbon carbon bonds on 24(25) would increase the anti-tumor and anti-metastasis activity of triterpene glycosides.In conclusion, Pearsonothria graeffei saponins could balance the peroxidation level, induce the tumor cell apoptosis of tumor cell and endothelial cell, reduce the factors related to metastasis and angiogenesis and finally prevent the growth and development of tumor. The relationship between structure and activity was compared. These may contribute to the exploitation and application of Pearsonothria graeffei.