Abstract
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.
Keywords: Bradykinin, peptide, xenotransplants, antagonists, metalloproteases
Current Pharmaceutical Design
Title: Bradykinin Antagonists as Anti-Cancer Agents
Volume: 9 Issue: 25
Author(s): J. M. Stewart
Affiliation:
Keywords: Bradykinin, peptide, xenotransplants, antagonists, metalloproteases
Abstract: 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.
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Cite this article as:
Stewart M. J., Bradykinin Antagonists as Anti-Cancer Agents, Current Pharmaceutical Design 2003; 9 (25) . https://dx.doi.org/10.2174/1381612033454171
DOI https://dx.doi.org/10.2174/1381612033454171 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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