Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like action.
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 gamma (PPARgamma) 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 PPARgamma activity of ARBs, luciferase assay using PSA promoter and PPARgamma 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.


CONCLUSIONS
The present study showed ARBs, especially those possessing a PPARgamma ligand-like structure, have a potential antagonistic effect on androgen-dependent and -independent prostate cancer.
Ishiguro
Hitoshi
H
Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama, Japan.
Ishiguro
Yukari
Y
Kubota
Yoshinobu
Y
Uemura
Hiroji
H
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000037:antagonists & inhibitors*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000473:pathology*; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases; D017430:Prostate-Specific Antigen; D000077333:Telmisartan