EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Background:Non-steroidal anti-inflammatory drugs inhibit the activity of cyclooxygenases (COXs), and their usage reduces the risks associated with prostate cancer. Celecoxib is a selective COX-2 inhibitor and reported to prevent the progression of prostate cancer. However, the mechanisms involved remain unclear. In this study, we investigated the suppression of prostate cancer growth by celecoxib and elucidated the biological relevance of the inhibited pathway in prostate cancer cell lines.Methods:Western blotting, quantitative real-time PCR and cell proliferation assay were used to resolve the mechanism of celecoxib in prostate cancer cell line PC3, LNCaP and their derivatives.Results:Celecoxib induced apoptosis and downregulated EP2, CREB and androgen receptor (AR). Moreover, EP2 antagonist downregulated CREB as well as COX-2 and AR, resulting in the suppression of cell proliferation. Furthermore, EP2 and CREB knockdown induced AR downregulation, indicating that AR suppression by celecoxib is mediated by EP2/CREB signaling.Conclusions:Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.

Original languageEnglish
Pages (from-to)10-17
Number of pages8
JournalProstate Cancer and Prostatic Diseases
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

Celecoxib
Androgen Receptors
Prostatic Neoplasms
Cell Proliferation
Down-Regulation
Cyclooxygenase 2
Cell Line
Cyclooxygenase 2 Inhibitors
Prostaglandin-Endoperoxide Synthases
Real-Time Polymerase Chain Reaction
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology
  • Cancer Research

Cite this

@article{5de6bde419bf486fa198ac41bbfd1cc8,
title = "EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer",
abstract = "Background:Non-steroidal anti-inflammatory drugs inhibit the activity of cyclooxygenases (COXs), and their usage reduces the risks associated with prostate cancer. Celecoxib is a selective COX-2 inhibitor and reported to prevent the progression of prostate cancer. However, the mechanisms involved remain unclear. In this study, we investigated the suppression of prostate cancer growth by celecoxib and elucidated the biological relevance of the inhibited pathway in prostate cancer cell lines.Methods:Western blotting, quantitative real-time PCR and cell proliferation assay were used to resolve the mechanism of celecoxib in prostate cancer cell line PC3, LNCaP and their derivatives.Results:Celecoxib induced apoptosis and downregulated EP2, CREB and androgen receptor (AR). Moreover, EP2 antagonist downregulated CREB as well as COX-2 and AR, resulting in the suppression of cell proliferation. Furthermore, EP2 and CREB knockdown induced AR downregulation, indicating that AR suppression by celecoxib is mediated by EP2/CREB signaling.Conclusions:Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.",
author = "Eiji Kashiwagi and masaki shiota and Akira Yokomizo and Junichi Inokuchi and Takeshi Uchiumi and S. Naito",
year = "2014",
month = "1",
day = "1",
doi = "10.1038/pcan.2013.53",
language = "English",
volume = "17",
pages = "10--17",
journal = "Prostate Cancer and Prostatic Diseases",
issn = "1365-7852",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer

AU - Kashiwagi, Eiji

AU - shiota, masaki

AU - Yokomizo, Akira

AU - Inokuchi, Junichi

AU - Uchiumi, Takeshi

AU - Naito, S.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background:Non-steroidal anti-inflammatory drugs inhibit the activity of cyclooxygenases (COXs), and their usage reduces the risks associated with prostate cancer. Celecoxib is a selective COX-2 inhibitor and reported to prevent the progression of prostate cancer. However, the mechanisms involved remain unclear. In this study, we investigated the suppression of prostate cancer growth by celecoxib and elucidated the biological relevance of the inhibited pathway in prostate cancer cell lines.Methods:Western blotting, quantitative real-time PCR and cell proliferation assay were used to resolve the mechanism of celecoxib in prostate cancer cell line PC3, LNCaP and their derivatives.Results:Celecoxib induced apoptosis and downregulated EP2, CREB and androgen receptor (AR). Moreover, EP2 antagonist downregulated CREB as well as COX-2 and AR, resulting in the suppression of cell proliferation. Furthermore, EP2 and CREB knockdown induced AR downregulation, indicating that AR suppression by celecoxib is mediated by EP2/CREB signaling.Conclusions:Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.

AB - Background:Non-steroidal anti-inflammatory drugs inhibit the activity of cyclooxygenases (COXs), and their usage reduces the risks associated with prostate cancer. Celecoxib is a selective COX-2 inhibitor and reported to prevent the progression of prostate cancer. However, the mechanisms involved remain unclear. In this study, we investigated the suppression of prostate cancer growth by celecoxib and elucidated the biological relevance of the inhibited pathway in prostate cancer cell lines.Methods:Western blotting, quantitative real-time PCR and cell proliferation assay were used to resolve the mechanism of celecoxib in prostate cancer cell line PC3, LNCaP and their derivatives.Results:Celecoxib induced apoptosis and downregulated EP2, CREB and androgen receptor (AR). Moreover, EP2 antagonist downregulated CREB as well as COX-2 and AR, resulting in the suppression of cell proliferation. Furthermore, EP2 and CREB knockdown induced AR downregulation, indicating that AR suppression by celecoxib is mediated by EP2/CREB signaling.Conclusions:Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.

UR - http://www.scopus.com/inward/record.url?scp=84894162326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894162326&partnerID=8YFLogxK

U2 - 10.1038/pcan.2013.53

DO - 10.1038/pcan.2013.53

M3 - Review article

C2 - 24518515

AN - SCOPUS:84894162326

VL - 17

SP - 10

EP - 17

JO - Prostate Cancer and Prostatic Diseases

JF - Prostate Cancer and Prostatic Diseases

SN - 1365-7852

IS - 1

ER -