The bacterial polysaccharide tecogalan blocks growth of breast cancer cells in vivo.
The growth of supportive tissue during the progression of solid tumors is an absolute requirement for the nourishment of the tumor. The blockade of this proliferative response of normal tissues to the growing tumor should hence inhibit tumor progression. We have shown earlier, that the heparinoid pentosan polysulfate (PPS) can block tumor growth and neoangiogenesis induced by Kaposi's FGF as well as by other heparin-binding growth factors (HBGFs). We now report on the effects of a bacterial polysaccharide, tecogalan, on tumor xenografts of human breast cancer cells. Tecogalan inhibited FGF-dependent SW-13 cells in vitro very similarly to PPS. Growth factor-independent MDA-MB 231 cells were used in animal studies to assess the in vivo potential of tecogalan. Subcutaneous growth of tumors was inhibited by once weekly i.v. administration of tecogalan. PPS single weekly administration showed a similar effect. No gross side effects were observed. Based on our previous studies with these models, we conclude, that tecogalan acts by blocking HBGFs released from tumor cells. Interestingly, single weekly dosing of either PPS or tecogalan appears to be strikingly more efficacious than spreading the dose over several administrations. These findings with a novel compound, tecogalan, and a novel treatment regimen, PPS, suggests a different approach to planning of therapies with these types of drugs.
Yunmbam
M K
MK
V.T. Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
Wellstein
A
A
D000230:Adenocarcinoma / Q000473:pathology*; D000310:Adrenal Gland Neoplasms / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011135:Polysaccharides, Bacterial; C079061:tecogalan; D010426:Pentosan Sulfuric Polyester