Perindopril: possible use in cancer therapy
Hitoshi Yoshiji1, Shigeki Kuriyama, Hiroshi Fukui
1Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
Abstract:
Since angiogenesis is essential for the growth of any solid tumor, emerging efforts are being made to develop antiangiogenic therapy. To date, however, no antiangiogenic agent has become widely available for the clinical setting. Angiotensin I-converting enzyme (ACE) inhibitors are commonly used as antihypertensive agents and it has recently been suggested that they decrease the risk of cancer. Studies have found that an ACE inhibitor, perindopril, is a potent inhibitor of experimental tumor development and angiogenesis at a clinically comparable dose. The potent angiogenic factor, vascular endothelial growth factor (VEGF), is significantly suppressed by perindopril and also inhibits VEGF-induced tumor growth. In vitro studies showed that perindopril is not cytotoxic to either tumor cells or endothelial cells. Since perindopril is already in widespread clinical use without serious side effects, it may represent a potential new strategy for anticancer therapy.
Insights
Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, effectively inhibits tumor growth and angiogenesis by suppressing vascular endothelial growth factor (VEGF). This widely used drug shows promise as a novel anticancer therapy due to its safety profile.
Area of Science:
- Oncology
- Pharmacology
- Cardiovascular Research
Background:
- Angiogenesis is crucial for solid tumor growth, driving the need for antiangiogenic therapies.
- Currently, no antiangiogenic agents are widely available for clinical use.
- Angiotensin-converting enzyme (ACE) inhibitors, used for hypertension, may reduce cancer risk.
Purpose of the Study:
- To investigate the antiangiogenic and antitumor effects of the ACE inhibitor perindopril.
- To determine if perindopril affects vascular endothelial growth factor (VEGF) levels and activity.
- To evaluate the potential of perindopril as an anticancer therapeutic strategy.
Main Methods:
- Experimental tumor development and angiogenesis models were used.
- In vitro studies assessed cytotoxicity to tumor and endothelial cells.
- Vascular endothelial growth factor (VEGF) levels and VEGF-induced tumor growth were analyzed.
Main Results:
- Perindopril demonstrated potent inhibition of experimental tumor development and angiogenesis at clinically relevant doses.
- Perindopril significantly suppressed vascular endothelial growth factor (VEGF).
- Perindopril did not exhibit cytotoxicity to tumor or endothelial cells in vitro.
Conclusions:
- Perindopril exhibits significant antiangiogenic and antitumor properties.
- Suppression of VEGF by perindopril contributes to its observed anticancer effects.
- Given its established safety profile, perindopril represents a potential new strategy for anticancer therapy.
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