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

Manish I. Patel, Kotha Subbaramaiah, Baoheng Du, Mindy Chang, Peiying Yang, Robert A. Newman, Carlos Cordon-Cardo, Howard T. Thaler, Andrew J. Dannenberg

Research output: Contribution to journalArticle

176 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1999-2007
Number of pages9
JournalClinical Cancer Research
Volume11
Issue number5
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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