Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells

The role of cyclooxygenase‐2 (COX‐2) and the mechanism by which it influences the development and behavior of prostate cancer is unclear. Selective COX‐2 inhibitors may be effective against prostate cancer via COX‐2‐independent mechanisms. But administration of high doses of COX‐2 inhibitors over lo...

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Bibliographic Details
Published in:International journal of cancer 2006-10, Vol.119 (7), p.1586-1598
Main Authors: Narayanan, Narayanan K., Narayanan, Bhagavathi A., Bosland, Maarten, Condon, Mark S., Nargi, Dominick
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Apoptosis - drug effects
Biological and medical sciences
Celecoxib
Cell Line, Tumor
COX‐2 inhibitor
docosahexaenoic acid
Docosahexaenoic Acids - pharmacology
Down-Regulation - drug effects
Electrophoresis, Gel, Two-Dimensional
Enzyme Activation - drug effects
General aspects
Heat-Shock Proteins - metabolism
HSP70 Heat-Shock Proteins - metabolism
Isoenzymes - metabolism
Male
Medical sciences
Molecular Chaperones - metabolism
Nitric Oxide Synthase Type II - metabolism
n‐3 PUFA
Pharmacology. Drug treatments
prostate cancer
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Protein Disulfide-Isomerases - metabolism
proteomics
Pyrazoles - pharmacology
Rats
Sulfonamides - pharmacology
Tumor Suppressor Protein p53 - metabolism
Tumors
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Summary:The role of cyclooxygenase‐2 (COX‐2) and the mechanism by which it influences the development and behavior of prostate cancer is unclear. Selective COX‐2 inhibitors may be effective against prostate cancer via COX‐2‐independent mechanisms. But administration of high doses of COX‐2 inhibitors over longer period of time may not be devoid of side effects. There is increasing interest in using COX‐2 inhibitors in combination with other chemopreventive agents to overcome the issue of toxicity. However, the molecular mechanisms underlying their combined actions are not well understood. Therefore, the present study was designed to determine the effects of low doses of docosahexaenoic acid (DHA) in combination with celecoxib on the molecular targets at the proteins level in rat prostate cancer cells. Two‐dimensional gel electrophoresis, in combination with mass spectrometry analysis, was used for protein identification. Western blot analysis confirmed the proteins identified. Paraffin‐embedded tissue sections from the rat prostate tumor were used to detect base level expression of heat shock protein 70 (HSP70) and p53. The rate of cancer cell growth was inhibited more effectively (p < 0.01) by DHA in combination with celecoxib at lower doses (2.5 μM each). A total number of twelve proteins were differentially expressed by the combined action of DHA and celecoxib at low doses. It was interesting to note that these agents activated both HSP70 and p53 proteins. Activation of HSP70 by the combined actions of DHA and celecoxib in the presence of wild‐type p53 reveals a unique COX‐2 independent mode of action against prostate cancer. © 2006 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.22031