Celecoxib inhibits prostate cancer growth: Evidence of a cyclooxygenase-2-independent mechanism Journal Article

  


Authors: Patel, M. I.; Subbaramaiah, K.; Du, B.; Chang, M.; Yang, P.; Newman, R. A.; Cordon-Cardo, C.; Thaler, H. T.; Dannenberg, A. J.
Article Title: Celecoxib inhibits prostate cancer growth: Evidence of a cyclooxygenase-2-independent mechanism
Abstract: Purpose: Selective cyclooxygenase-2 (COX-2) inhibitors may suppress carcinogenesis by both COX-2-dependent and COX-2-independent mechanisms. The primary purpose of this study was to evaluate whether celecoxib or rofecoxib, two widely used selective COX-2 inhibitors, possess COX-2-independent antitumor activity. Experimental Design: PC3 and LNCaP human prostate cancer cell lines were used to investigate the growth inhibitory effects of selective COX-2 inhibitors in vitro. To complement these studies, we evaluated the effect of celecoxib on the growth of PC3 xenografts. Results: COX-1 but not COX-2 was detected in PC3 and LNCaP cells. Clinically achievable concentrations (2.5-5.0 μmol/L) of celecoxib inhibited the growth of both cell lines in vitro, whereas rofecoxib had no effect over the same concentration range. Celecoxib inhibited cell growtli by inducing a G1 cell cycle block and reducing DNA synthesis. Treatment with celecoxib also led to dose-dependent inhibition of PC3 xenograft growth without causing a reduction in intratumor prostaglandin E2. Inhibition of tumor growth occurred at concentrations (2.37-5.70 μmol/L) of celecoxib in plasma that were comparable with the concentrations required to inhibit cell growth in vitro. The highest dose of celecoxib led to a 52% reduction in tumor volume and an ∼50% decrease in both cell proliferation and microvessel density. Treatment with celecoxib caused a marked decrease in amounts of cyclin D1 both in vitro and in vivo. Conclusions: Two clinically available selective COX-2 inhibitors possess different COX-2-independent anticancer properties. The anticancer activity of celecoxib may reflect COX-2-independent in addition to COX-2-dependent effects. ©2005 American Association for Cancer Research.
Keywords: controlled study; human cell; dose response; nonhuman; cell proliferation; mouse; animals; mice; animal tissue; cell growth; tumor volume; animal experiment; animal model; membrane proteins; antineoplastic activity; cancer cell culture; tumor xenograft; tumor cells, cultured; drug selectivity; prostate cancer; prostatic neoplasms; cancer inhibition; mice, nude; celecoxib; cyclooxygenase 2 inhibitor; cyclooxygenase 2 inhibitors; pyrazoles; sulfonamides; cyclooxygenase 2; rofecoxib; cyclooxygenase 1; prostaglandin e2; transplantation, heterologous; drug blood level; cyclin d1; microvasculature; cell cycle g1 phase; dna synthesis inhibition; concentration response; sulfones; lactones; prostaglandin-endoperoxide synthases; cyclooxygenase inhibitors
Journal Title: Clinical Cancer Research
Volume: 11
Issue: 5
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2005-03-01
Start Page: 1999
End Page: 2007
Language: English
DOI: 10.1158/1078-0432.ccr-04-1877
PUBMED: 15756026
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-16344389993&partnerID=40&md5=9140e76e2bf97ba93508b5c39495de0e
Notes: --- - "Cited By (since 1996): 121" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Manish Patel
    11 Patel
  2. Carlos Cordon-Cardo
    612 Cordon-Cardo
  3. Howard T Thaler
    245 Thaler
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