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Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator‐activated receptor gamma ligand like action
Author(s) -
Ishiguro Hitoshi,
Ishiguro Yukari,
Kubota Yoshinobu,
Uemura Hiroji
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20571
Subject(s) - telmisartan , prostate cancer , cancer research , angiotensin ii , peroxisome proliferator activated receptor , cell growth , receptor , prostate , endocrinology , medicine , chemistry , biology , cancer , biochemistry , blood pressure
BACKGROUND We previously reported that angiotensin II (AII) activated the proliferation of prostate cancer cells, and its antagonist, an AII receptor type 1 (AT1R) blocker (ARB), inhibited the proliferation of prostate cancer in vitro and in vivo. In the present study, we investigated whether telmisartan, an ARB, has a unique feature as a peroxisome proliferator‐activated receptor γ (PPARγ) ligand, and its suppressive potential on prostate cancer cells. METHODS Cell count or MTT assay were carried out for growth suppression of prostate cancer cells. Phosphorylation of mitogen‐activated protein kinase (MAPK), specific expression of prostate specific antigen (PSA) and AT1R were investigated by western blot. To confirm the PPARγ activity of ARBs, luciferase assay using PSA promoter and PPARγ response elements (PPRE) plasmids was performed. RESULTS The results showed that cell proliferation and signal transduction were inhibited by telmisartan treatment. Also, inhibition of PSA expression by telmisartan was confirmed by western blot and luciferase assay, indicating that an ARB acted in a similar way such as an anti‐androgenic agent in prostate cancer cells. CONCLUSION The present study showed ARBs, especially those possessing a PPARγ ligand‐like structure, have a potential antagonistic effect on androgen‐dependent and ‐independent prostate cancer. Prostate 67: 924–932, 2007. © 2007 Wiley‐Liss, Inc.