NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells

Molykutty John-Aryankalayil, Sanjeewani T. Palayoor, David Cerna, Michael T. Falduto, Scott R. Magnuson, C. Norman Coleman

Research output: Contribution to journalArticle

Abstract

Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal anti-inflammatory drugs (NSAID) exhibit potent anticancer effects in vitro and in vivo by COX-2-dependent and COX-2-independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2-specific NSAID NS-398 (0.01 and 0.1 mmol/L), a nonspecific NSAID ibuprofen (0.1 and 1.5 mmol/L) and RNA interference (RNAi)-mediated COX-2 inhibition in PC3 prostate cancer cells. A total of 3,362 differentially expressed genes with 2-fold change and P <0.05 were identified. Low concentrations of NSAIDs and COX-2 RNAi altered very few genes (1-3%) compared with the higher concentration of NS-398 (17%) and ibuprofen (80%). Ingenuity Pathway Analysis was used for distributing the differentially expressed genes into biological networks and for evaluation of functional significance. The top 3 networks for both NSAIDs included functional categories of DNA replication, recombination and repair, and gastrointestinal disease. Immunoresponse function was specific to NS-398, and cell cycle and cellular movement were among the top functions for ibuprofen. Ingenuity Pathway Analysis also identified renal and urologic disease as a function specific for ibuprofen. This comprehensive study identified several COX-2-independent targets of NSAIDs, which may help explain the antitumor and radiosensitizing effects of NSAIDs. However, none of these categories were reflected in the identified networks in PC3 cells treated with clinically relevant low concentrations of NS-398 and ibuprofen or with COX-2 RNAi, suggesting the benefit to fingerprinting preclinical drug concentrations to improve their relevance to the clinical setting.

Original languageEnglish (US)
Pages (from-to)261-273
Number of pages13
JournalMolecular Cancer Therapeutics
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Ibuprofen
Cyclooxygenase 2
RNA Interference
Transcriptome
Prostatic Neoplasms
Non-Steroidal Anti-Inflammatory Agents
Anti-Inflammatory Agents
Pharmaceutical Preparations
Radiation-Sensitizing Agents
Genes
Urologic Diseases
Recombinational DNA Repair
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Gastrointestinal Diseases
Microarray Analysis
DNA Replication
DNA Repair
Cell Cycle
Kidney

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells. / John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Falduto, Michael T.; Magnuson, Scott R.; Coleman, C. Norman.

In: Molecular Cancer Therapeutics, Vol. 8, No. 1, 01.01.2009, p. 261-273.

Research output: Contribution to journalArticle

John-Aryankalayil, Molykutty ; Palayoor, Sanjeewani T. ; Cerna, David ; Falduto, Michael T. ; Magnuson, Scott R. ; Coleman, C. Norman. / NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells. In: Molecular Cancer Therapeutics. 2009 ; Vol. 8, No. 1. pp. 261-273.
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