Abstract
Acidic mucopolysaccharide from Holothuria Leucospilota (HS) may affect some steps in metastasis cascade. In vitro, HS inhibited the growth of B16F10 cells and proliferation of VEGF-induced HUVEC dose-dependently compared to the control, VEGF-induced capillary-like tube networks and the numbers of migratory and invasive cells were significantly inhibited by HS in a dose-dependent manner under the cytotoxic doses. Additionally, VEGF-induced vessel sprouting of rat aortic ring was also inhibited by HS. It also has been demonstrated that the invasive ability of B16F10 melanoma cells through the Matrigel-embedded Boyden chamber was suppressed by 0.5 muM HS. The protein level secreted by B16F10 cells of MMP-2,-9 and VEGF were decreased by HS treatment. In vivo, a tumor growth inhibition study was carried out using mice bearing B16F10 cells model of metastasis, no matter experimental or spontaneous, showed that HS at 5.2, 11.6 and 26 mg/kg (weight of mice) could markedly decreased the metastatic tumors in mouse lung in a dose-dependent manner. In CAM assay and Matrigel plug assay in vivo, HS (50 microg/egg and 100 microg/egg) inhibited new blood vessel formation on the growing chick chorioallantoic membrane, and HS (5.2 and 26 mg/kg body weight) reduced the vessel density in Matrigel plugs implanted in mice. Taken together, these results demonstrate that HS has antimetastasic properties possibly via its antiangiogenesis induced by downregulation of VEGF and suppression of invasive ability of cancer cells mediated by downregulation of MMP-2, -9 and their activities.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Angiogenesis Inhibitors / isolation & purification*
-
Angiogenesis Inhibitors / pharmacology
-
Angiogenesis Inhibitors / therapeutic use
-
Animals
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / isolation & purification
-
Antineoplastic Agents / pharmacology*
-
Antineoplastic Agents / therapeutic use
-
Aorta / drug effects
-
Cell Line / cytology
-
Cell Line / drug effects
-
Cell Line, Tumor / cytology
-
Cell Line, Tumor / drug effects
-
Cell Movement / drug effects
-
Drug Screening Assays, Antitumor
-
Endothelial Cells / cytology
-
Endothelial Cells / drug effects
-
Glycosaminoglycans / chemistry
-
Glycosaminoglycans / isolation & purification
-
Glycosaminoglycans / pharmacology*
-
Glycosaminoglycans / therapeutic use
-
Holothuria / chemistry*
-
Humans
-
Lung Neoplasms / prevention & control
-
Lung Neoplasms / secondary
-
Matrix Metalloproteinase 2 / biosynthesis
-
Matrix Metalloproteinase 2 / genetics
-
Matrix Metalloproteinase 9 / biosynthesis
-
Matrix Metalloproteinase 9 / genetics
-
Melanoma, Experimental / drug therapy*
-
Melanoma, Experimental / pathology
-
Melanoma, Experimental / secondary
-
Mice
-
Mice, Inbred C57BL
-
Neoplasm Invasiveness / prevention & control*
-
Neoplasm Proteins / biosynthesis
-
Neoplasm Proteins / genetics
-
Rats
-
Vascular Endothelial Growth Factor A / biosynthesis
-
Vascular Endothelial Growth Factor A / genetics
Substances
-
Angiogenesis Inhibitors
-
Antineoplastic Agents
-
Glycosaminoglycans
-
Neoplasm Proteins
-
Vascular Endothelial Growth Factor A
-
vascular endothelial growth factor A, mouse
-
Matrix Metalloproteinase 2
-
Matrix Metalloproteinase 9