Antiangiogenic and antitumoral properties of a polysaccharide isolated from the seaweed Sargassum stenophyllum.
The potential antiangiogenic and antitumoral properties of SargA, a polysaccharide extracted from the brown marine alga Sargassum stenophyllum, were studied in assays carried out in chick embryos and mice. Gelfoam plugs containing SargA (2-1500 microg/plug) implanted in vivo into fertilized 6-day-old chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). By day 8, the highest dose of SargA alone decreased the vessel number in the CAM by 64%, but coadministered with hydrocortisone (156 microg/plug, which alone caused 30% inhibition) failed to potentiate its antiangiogenic effect. Combined with basic fibroblast growth factor (50 ng/plug), SargA (1500 microg/plug) abolished angiogenesis stimulated by this factor in both chick embryo CAM and in subcutaneous (s.c.) Gelfoam plugs implanted in the dorsal skin of Swiss mice (measured as plug hemoglobin content). Repeated s.c. injections of SargA (1.5 or 150 microg per animal per day for 3 days) close to B16F10 melanoma cell tumors in the dorsal skin of mice markedly decreased tumor growth in a dose-related fashion (by 40% and 80% at 2 weeks after the first injection, respectively), without evident signs of toxicity. SargA caused graded inhibitions of migration and viability of cultured B16F10 cells and also displayed antithrombotic activity in human plasma (5 mg/ml increased thrombin time 2.5-fold relative to saline). Thus, SargA exhibits pronounced antiangiogenic as well as antitumoral properties. Although the latter action of SargA might be related to the inhibition of angiogenesis, the polysaccharide also exerts cytotoxic effects on tumor cells. Because of its chemical characteristics and polyanionic constituents, we postulate that the polysaccharide SargA might modulate the activity of heparin-binding angiogenic growth factors.
Dias
Paulo Fernando
PF
Departament of Pharmacology, Biological Sciences Center Block D, Federal University of Santa Catarina, University Campus - Trindade, Florianópolis, CEP 88.049-900, SC, Brazil.
Siqueira
Jarbas Mota
JM
Vendruscolo
Luiz Felipe
LF
de Jesus Neiva
Teresinha
T
Gagliardi
Antônio Ricardo
AR
Maraschin
Marcelo
M
Ribeiro-do-Valle
Rosa Maria
RM
D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D002642:Chick Embryo; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D011134:Polysaccharides / Q000302:isolation & purification / Q000627:therapeutic use*; D044647:Sargassum; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011134:Polysaccharides