Angiotensin-I converting enzyme inhibitors as potential anti-angiogenic agents for cancer therapy.
Angiotensin-I converting enzyme inhibitors (ACE-Is) are commonly used as safe antihypertensive agents, and it has recently been suggested that they decrease the risk of cancer development. Recent studies have revealed that the renin-angiotensin system (RAS) is involved in the development of many types of tumor. Angiotensin-II (AT-II) has many biological effects, including neo-vascularization, which plays a pivotal role in tumor development. AT-II induces a potent angiogenic factor, namely the vascular endothelial growth factor (VEGF). Some studies have proven that several ACE-Is are potent inhibitors of experimental tumor development and angiogenesis at clinically comparable doses. VEGF expression in tumors is also significantly suppressed by ACE-Is. When used in combination with the conventional anti-cancer drugs, ACE-Is exert more potent anti-tumor activities as compared with either single agent, in addition to suppression of the intra-tumoral angiogenesis. Furthermore, ACE-Is reportedly not only suppress tumor growth but also attenuate the carcinogenesis process in which angiogenesis is involved. Since ACE-Is are already in widespread clinical case without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention.
Yoshiji
Hitoshi
H
Third Department of Internal Medicine, Nara Medical University, Nara, Japan. yoshijih@naramed-u.ac.jp
Kuriyama
Shigeki
S
Noguchi
Ryuichi
R
Fukui
Hiroshi
H
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A