The effect of fibrinogen-methotrexate derivatives on HeLa cell growth.
Proteolytic cleavage of bovine fibrinogen with covalently bound methotrexate (MTX) was studied using four different proteolytic enzymes--trypsin, chymotrypsin, pepsin, and cathepsin D and the interaction of the modified fibrinogen (or fibrin) with HeLa cells was investigated. The presence of fibrin-MTX derivative did not induce any significant morphological alternations of cells. The fibrin-MTX derivative in the gel form was solubilized easily by the action of all proteinases investigated, hydrolysis of highly crosslinked denatured fibrin-MTX in suspension proceeded slower. The solubilized fibrin-MTX degradation products had a strong inhibiting effect on the growth of HeLa cells cultured in monolayer indicating the liberation of chemotherapeutically active MTX from its fibrin derivative.
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D005340:Fibrinogen / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins; D007700:Kinetics; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000494:pharmacology; D010447:Peptide Hydrolases
D000922:Immunotoxins; C049996:fibrinogen-methotrexate conjugate; D005340:Fibrinogen; D010447:Peptide Hydrolases; D008727:Methotrexate