Mode of action of razoxane: inhibition of basement membrane collagen-degradation by a malignant tumor enzyme.
Razoxane is an antitumor agent structurally related to EDTA. Its cytotoxic mechanism of action has been shown to involve interference with cell division and reduction of the gross rate of DNA synthesis. In this study we present evidence that razoxane, at therapeutically attainable concentrations, inhibits type IV collagen and basement membrane degradation by an enzyme isolated from malignant tumors. This effect is attributed to the chelating properties of razoxane and may explain the antimetastatic properties, by means of stabilization of tumor blood vessels, which have been associated with the action of the antitumor drug.
Karakiulakis
G
G
Department of Pharmacology, University of Patras Medical School, Greece.
Missirlis
E
E
Maragoudakis
M E
ME
D000107:Acetylation; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000201:enzymology; D002417:Cattle; D003013:Clostridium / Q000201:enzymology; D003094:Collagen / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011929:Razoxane / Q000494:pharmacology*
D010879:Piperazines; D011929:Razoxane; D003094:Collagen; D003012:Microbial Collagenase