Next Article in Journal
Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis
Previous Article in Journal
Protein Intake, Nutritional Status and Outcomes in ICU Survivors: A Single Center Cohort Study
Previous Article in Special Issue
The Importance of Time to Prostate-Specific Antigen (PSA) Nadir after Primary Androgen Deprivation Therapy in Hormone-Naïve Prostate Cancer Patients
Article Menu

Export Article

Open AccessArticle
J. Clin. Med. 2019, 8(1), 44; https://doi.org/10.3390/jcm8010044

Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest

1
Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
2
Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
3
Laboratory of Community Pharmacy, Gifu Pharmaceutical University, Gifu, Gifu 501-1196, Japan
*
Author to whom correspondence should be addressed.
Received: 11 December 2018 / Revised: 25 December 2018 / Accepted: 28 December 2018 / Published: 4 January 2019
Full-Text   |   PDF [1675 KB, uploaded 4 January 2019]   |  

Abstract

Pirfenidone (PFD) is an anti-fibrotic drug used to treat idiopathic pulmonary fibrosis by inducing G1 cell cycle arrest in fibroblasts. We hypothesize that PFD can induce G1 cell cycle arrest in different types of cells, including cancer cells. To investigate the effects of PFD treatment on the growth of human prostate cancer (PCa) cells, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines (androgen-low-sensitive E9 and F10 cells and androgen-insensitive AIDL cells), as well as an androgen-insensitive human PCa cell line (PC-3). PFD treatment suppressed the growth of all PCa cells. Transforming growth factor β1 secretion was significantly increased in PFD-treated PCa cells. In both LNCaP and PC-3 cells, PFD treatment increased the population of cells in the G0/G1 phase, which was accompanied by a decrease in the S/G2 cell population. CDK2 protein expression was clearly decreased in PFD-treated LNCaP and PC-3 cells, whereas p21 protein expression was increased in only PFD-treated LNCaP cells. In conclusion, PFD may serve as a novel therapeutic drug that induces G1 cell cycle arrest in human PCa cells independently of androgen sensitivity. Thus, in the tumor microenvironment, PFD might target not only fibroblasts, but also heterogeneous PCa cells of varying androgen-sensitivity levels. View Full-Text
Keywords: prostate cancer; androgen sensitivity; pirfenidone; TGFβ1; G1 cell cycle arrest prostate cancer; androgen sensitivity; pirfenidone; TGFβ1; G1 cell cycle arrest
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Ishii, K.; Sasaki, T.; Iguchi, K.; Kato, M.; Kanda, H.; Hirokawa, Y.; Arima, K.; Watanabe, M.; Sugimura, Y. Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest. J. Clin. Med. 2019, 8, 44.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top