Study on anti-metastasis of heparin derivatives as ligand antagonist of p-selectin.
Heparin has a potential value as therapeutic agents that block P-selectin-mediated cell adhesion and prevent tumor metastasis. However, the strong anticoagulant potency limits its applicability for the anti-metastasis activity. Carboxyl and sulfate groups of heparin are closely related to its anticoagulant activity, so seven kinds of heparin derivatives related to carboxyl and sulfate groups were prepared, and their effects on anti-metastasis as ligand antagonist of p-selectin were studied. The results showed that heparin, carboxyl reduction heparin, 2-O-desulfated heparin and N-desulfated- N-acetylated heparin could inhibit the adhesion of tumor cells to endothelial cells and platelets effectively as ligand antagonist of P-selectin.
Li
Y
Y
Institute of Biochemical and Biotechnological Drugs, Shandong University, Jinan 250012, China.
Luo
J-Y
JY
Cui
H-F
HF
Zheng
L
L
Du
S-S
SS
D000925:Anticoagulants / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D009362:Neoplasm Metastasis; D019007:P-Selectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology
D000925:Anticoagulants; D008024:Ligands; D019007:P-Selectin; D006493:Heparin