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Article

Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis

by
Shugo Suzuki
1,2,*,
Yukiko Mori
1,
Aya Nagano
1,
Aya Naiki-Ito
1,
Hiroyuki Kato
1,
Yuko Nagayasu
1,
Mizuho Kobayashi
1,
Toshiya Kuno
1 and
Satoru Takahashi
1
1
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
2
Pathology Division, Nagoya City East Medical Center, Nagoya 464-8547, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2016, 17(12), 2071; https://doi.org/10.3390/ijms17122071
Submission received: 29 September 2016 / Revised: 24 November 2016 / Accepted: 2 December 2016 / Published: 10 December 2016
(This article belongs to the Section Bioactives and Nutraceuticals)
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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.
Keywords: peroxisome proliferator-activated receptor γ; pioglitazone; prostate; carcinogenesis; prostate cancer; nuclear factor κB peroxisome proliferator-activated receptor γ; pioglitazone; prostate; carcinogenesis; prostate cancer; nuclear factor κB

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MDPI and ACS Style

Suzuki, S.; Mori, Y.; Nagano, A.; Naiki-Ito, A.; Kato, H.; Nagayasu, Y.; Kobayashi, M.; Kuno, T.; Takahashi, S. Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis. Int. J. Mol. Sci. 2016, 17, 2071. https://doi.org/10.3390/ijms17122071

AMA Style

Suzuki S, Mori Y, Nagano A, Naiki-Ito A, Kato H, Nagayasu Y, Kobayashi M, Kuno T, Takahashi S. Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis. International Journal of Molecular Sciences. 2016; 17(12):2071. https://doi.org/10.3390/ijms17122071

Chicago/Turabian Style

Suzuki, Shugo, Yukiko Mori, Aya Nagano, Aya Naiki-Ito, Hiroyuki Kato, Yuko Nagayasu, Mizuho Kobayashi, Toshiya Kuno, and Satoru Takahashi. 2016. "Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis" International Journal of Molecular Sciences 17, no. 12: 2071. https://doi.org/10.3390/ijms17122071

APA Style

Suzuki, S., Mori, Y., Nagano, A., Naiki-Ito, A., Kato, H., Nagayasu, Y., Kobayashi, M., Kuno, T., & Takahashi, S. (2016). Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis. International Journal of Molecular Sciences, 17(12), 2071. https://doi.org/10.3390/ijms17122071

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