Anti-proliferative and antitumoral activities of a functionalized dextran (CMDBJ) on the 1205 L-U human tumor melanoma cells.
Carboxy methyl dextran benzylamide jorge (CMDBJ) is a derivatized dextran prepared from native dextran after random carboxymethylation of hydroxyl groups on D-glucose units (CM) and consecutive conversion of some carboxylate groups to benzylamide structures (B). This polymer exhibits an inhibitory action upon the proliferation of 1205 L-U human melanoma cells. At low concentrations, this compound exerts a cytostatic effect whereas, at higher concentrations, a cytotoxicity appears within 24 hours of treatment. The 1205 L-U cell line forms subcutaneous angiogenic tumors in athymic mice and, after several weeks, spontaneously forms micrometastasis in the lungs. We demonstrated that the CMDBJ treatment of animals not only reduces the rapid growth of primary tumors but also induces tumor regression and tumor necrosis. Moreover, CMDBJ treatment blocks the appearance of lung metastasis. Pleiotrophin (PTN), heparin-binding angiogenic growth factor, is secreted by 1205 L-U cells and breast tumor MDA-MB 231 cells. CMDBJ, as an inhibitor of heparin-binding growth factor activities, suppresses the mitogenic activity of conditioned media from 1205 L-U and MDA-MB 231 on endothelial HUVEC cells. We conclude that CMDBJ can inhibit the in vitro cell proliferation of 1205 L-U cells and 1205 L-U tumor development in athymic mice and that PTN secreted by these cells could be involved in this inhibition.
Bastias
Jorge
J
Laboratoire d' Oncologie Cellulaire et Moléculaire, UFR Léonard de Vinci, Université Paris XIII, Bobigny, France.
Wei
Ming X
MX
Huynh
Remi
R
Chaubet
Fréderic
F
Jozefonvicz
Jacqueline
J
Crepin
Michel
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003911:Dextrans / Q000032:analysis / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003911:Dextrans; D006131:Growth Inhibitors; C099253:CMDBS 25