Growth inhibition in vitro of murine mammary adenocarcinoma cells by heparin and chemically modified heparins

G. BERTOLESI,; L. LAURIA,; E.S.DE LUSTIG,; A.M.EIJÁN

TUMOR BIOLOGY

KARGER

Año: 1994 vol. 15 p. 275 - 283

1010-4283

25. Tumour Biol. 1994;15(5):275-83. Growth inhibition in vitro of murine mammary adenocarcinoma cells by heparin and chemically modified heparins. Bertolesi GE, Lauría de Cidre L, Eiján AM. Area de Investigaciones, Instituto de Oncología A.H. Roffo, Universidad de BuenosAires, Argentina. Heparin, a highly sulfated polysaccharide used as an antithrombotic andanticoagulant, inhibits proliferation of several cell types. We have investigatedthe effect of heparin and chemically modified heparins on the growth of a cellculture 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 differentanticoagulant properties showed a similar antiproliferative effect. Histological assays showed that heparin was internalized and appeared in cytoplasmicvesicules. O-desulfated, O/N-desulfated N-acetylated and N-desulfated heparinslost their antiproliferative activity, while N-desulfated N-acetylated heparinsignificantly inhibited cell proliferation with or without FCS. The finding of anantiproliferative action of N-desulfated N-acetylated heparin which does not showanticoagulant activity suggests a possible therapeutic role for this compound as an antineoplastic drug.  PMID: 7991988 [PubMed - indexed for MEDLINE]