Growth inhibition in vitro of murine mammary adenocarcinoma cells by heparin and chemically modified heparins.
Heparin, a highly sulfated polysaccharide used as an antithrombotic and anticoagulant, inhibits proliferation of several cell types. We have investigated the effect of heparin and chemically modified heparins on the growth of a cell culture of a murine mammary adenocarcinoma (M3). We found that heparin inhibited the proliferation of M3 cells growing either with or without 2% fetal calf serum (FCS) in a dose-dependent and reversible fashion. Several heparins with different anticoagulant properties showed a similar antiproliferative effect. Histological assays showed that heparin was internalized and appeared in cytoplasmic vesicules. O-desulfated, O/N-desulfated N-acetylated and N-desulfated heparins lost their antiproliferative activity, while N-desulfated N-acetylated heparin significantly inhibited cell proliferation with or without FCS. The finding of an antiproliferative action of N-desulfated N-acetylated heparin which does not show anticoagulant activity suggests a possible therapeutic role for this compound as an antineoplastic drug.
Bertolesi
G E
GE
Area de Investigaciones, Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Argentina.
Lauría de Cidre
L
L
Eiján
A M
AM
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000473:pathology; D006493:Heparin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D014407:Tumor Cells, Cultured
D006493:Heparin