title: Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis.
abstract: Pioglitazone (PGZ), a peroxisome proliferator-activated receptor γ agonist, which is known as a type 2 diabetes drug, inhibits cell proliferation in various cancer cell lines, including prostate carcinomas. This study focused on the effect of PGZ on prostate carcinogenesis using a transgenic rat for an adenocarcinoma of prostate (TRAP) model. Adenocarcinoma lesions as a percentage of overall lesions in the ventral prostate were significantly reduced by PGZ treatment in a dose-dependent manner. The number of adenocarcinomas per given area in the ventral prostate was also significantly reduced by PGZ treatment. The Ki67 labeling index in the ventral prostate was also significantly reduced by PGZ. Decreased cyclin D1 expression in addition to the inactivation of both p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)κB were detected in PGZ-treated TRAP rat groups. In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB. The suppression of cultured cell growth was mainly regulated by the NFκB pathway as detected using specific inhibitors in both LNCaP and PC3, a human androgen-independent prostate cancer cell line. These data suggest that PGZ possesses a chemopreventive potential for prostate cancer.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. shugo@med.nagoya-cu.ac.jp.|Pathology Division, Nagoya City East Medical Center, Nagoya 464-8547, Japan. shugo@med.nagoya-cu.ac.jp.
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. ymori345@gmail.com.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. me_me_sheep3@yahoo.co.jp.
authors.forename: Aya
authors.initials: A
authors.lastname: Nagano
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. ayaito@med.nagoya-cu.ac.jp.
authors.forename: Aya
authors.initials: A
authors.lastname: Naiki-Ito
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. h.kato@med.nagoya-cu.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. naga-p@dk.pdx.ne.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagayasu
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. k-miz@topaz.ocn.ne.jp.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. tkuno@med.nagoya-cu.ac.jp.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kuno
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. sattak@med.nagoya-cu.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D048051:p38 Mitogen-Activated Protein Kinases; D000077205:Pioglitazone
keywords: carcinogenesis; nuclear factor κB; peroxisome proliferator-activated receptor γ; pioglitazone; prostate; prostate cancer