Bradykinin antagonists as anti-cancer agents.
The nonapeptide bradykinin is an important growth factor for many cancers. Certain peptide and non-peptide bradykinin antagonists show remarkable anti-cancer activities in both in vitro and in vivo cancer models, especially of lung and prostate cancers. Bradykinin antagonists stimulate apoptosis in cancers by a novel "biased agonist" mechanism: they block intracellular increase of calcium concentration but stimulate the MAP kinase pathway. This unbalanced effect stimulates caspase activation. In nude mouse xenotransplants of lung and prostate cancers the antagonists inhibit angiogenesis and activation of membrane metalloproteases (MMP 2 and 9). In the xenotransplants certain bradykinin antagonists showed higher potency than standard anti-cancer drugs, without evident toxicity to the hosts. These compounds offer great promise for development of new anti-cancer drugs.
Stewart
J M
JM
Department of Biochemistry and Molecular Genetics University of Colorado School of Medicine 4200 E. Ninth Ave. Denver, CO 80262 USA. john.stewart@uchsc.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D001920:Bradykinin