Antiproliferative efficacy of angiotensin II receptor blockers in prostate cancer.
An apparent low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors is reported; however, the molecular mechanisms have not been elucidated. Angiotensin-II (Ang-II) is well known to be associated with hypertension, as a main peptide of the renin-angiotensin system, and its detailed molecular mechanisms have recently been elucidated. For instance, Ang-II directly activates the mitogenic signal transduction pathway through the angiotensin-II type-1 (AT1) receptor in smooth muscle cells and cardiac myocytes. Ang-II receptor blockers (ARBs), a class of antihypertensive agent, suppress signal transduction pathways mediated by growth factors such as epidermal growth factor (EGF), through the AT1 receptor. Our studies demonstrated that an ARB had the potential for antiproliferative effects and inhibition of angiogenesis in prostate cancer cells. The AT1 receptor is categorized in the guanosine phosphate binding protein-coupled receptors (GPCRs), which are viewed as critical regulators of the interactions between epithelial and stromal cells. Hence, we consider that in overcoming prostate cancer, it is very important to inhibit GPCR signaling in cancer cells by ARBs. It is unclear how prostate cancer growth changes from being hormone dependent to independent, and no effective therapy has therefore been developed. Our clinical data revealed that ARB administration decreased prostate specific antigen (PSA) and improved performance status in patients with hormone-refractory prostate cancer. This review provides an insight into the key role of Ang-II and the possibility of ARBs for molecular targeting of mitogenesis and angiogenesis in prostate cancer.
Uemura
Hiroji
H
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. hu0428@med.yokohama-cu.ac.jp
Nakaigawa
Noboru
N
Ishiguro
Hitoshi
H
Kubota
Yoshinobu
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011467:Prostate / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin