Related Experiment Videos
Bradykinin antagonists as new drugs for prostate cancer
John M Stewart1, Daniel C Chan, Vitalija Simkeviciene
1Department of Biochemistry, University of Colorado School of Medicine, Denver, CO 80262, USA. john.stewart@uchsc.edu
Abstract:
Bradykinin (BK) is an autocrine growth factor for lung and prostate cancers. BK also facilitates tumor extension by increasing tissue permeability and stimulating angiogenesis. Peptide BK antagonists are in development as potential new drugs for lung cancer. Newer nonpeptide BK antagonists have even higher potency against lung cancer, in vitro and in vivo. These compounds have now been applied to the study of prostate cancers, and have been found to be effective. Prostate cancer cell line PC3 is derived from a late-stage, hormone-independent, metastatic tumor; its growth is difficult to inhibit. Our established BK antagonists, while less effective against this line of prostate cancer in xenografts in nude mice than against lung cancer, are active and have led the way to development of new peptide and nonpeptide agents for prostate cancer. In addition to inhibiting cancer cell growth directly, they inhibit angiogenesis mediated by vascular endothelial growth factor, and inhibit increased tissue permeability mediated by membrane metalloproteases in these tumors. This class of compounds offers hope for development of new drugs for refractory prostate cancer.
Insights
Bradykinin antagonists show promise for treating prostate cancer. These compounds inhibit tumor growth, angiogenesis, and tissue permeability, offering hope for new refractory prostate cancer drugs.
Area of Science:
- Oncology
- Pharmacology
Background:
- Bradykinin (BK) acts as an autocrine growth factor in lung and prostate cancers.
- BK promotes tumor progression by increasing vascular permeability and angiogenesis.
Purpose of the Study:
- To investigate the efficacy of bradykinin (BK) antagonists in treating prostate cancer.
- To explore the potential of novel peptide and nonpeptide BK antagonists for refractory prostate cancer.
Main Methods:
- Application of established and novel BK antagonists to prostate cancer models, including the PC3 cell line.
- Evaluation of antagonist effects on cancer cell growth, angiogenesis, and tissue permeability in vitro and in vivo.
Main Results:
- BK antagonists demonstrated activity against prostate cancer, including the aggressive PC3 cell line.
- Compounds inhibited tumor growth, vascular endothelial growth factor-mediated angiogenesis, and membrane metalloprotease-driven tissue permeability.
Conclusions:
- BK antagonists are effective against prostate cancer and offer a promising therapeutic strategy.
- These agents provide a new avenue for developing drugs for hormone-independent and metastatic prostate cancers.