Induction of the p75NTR by Aryl Propionic Acids in Prostate Cancer Cells

Abstract

The p75 neurotrophin receptor (p75NTR) is a tumor suppressor in the prostate whose expression decreases as prostate cancer progresses. The purpose of this project is to investigate the role of p75NTR in the observed anticancer activity of aryl propionic acids in the prostate. It has been demonstrated that treatment of prostate cancer cells with the aryl propionic acids R-flurbiprofen and ibuprofen induces reexpression of p75NTR, decreases cell survival, and increases apoptosis. Investigation into the mechanism of p75NTR induction by R-flurbiprofen and ibuprofen revealed a strong correlation between increased p75NTR protein level and increased p75NTR mRNA level. Finally, induction of p75NTR seems to be dependent on the p38 MAPK pathway, which is involved in regulating mRNA stability of a subset of transcripts. Using the 2-phenyl propionic acid moiety of these profens as a pharmacophore, an in silico database of 30 million compounds was screened and carprofen was additionally identified as having activity for induction of p75NTR levels and inhibition of cell survival.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2008
Accession Number
ADA508209

Entities

People

  • Shehla Wynne

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Antineoplastic Agents
  • Apoptosis
  • Blood
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Chemistry
  • Epithelial Cells
  • Gene Expression
  • Growth Factors
  • Health Services
  • Neoplasms
  • Peptides
  • Propionic Acid
  • Prostate Cancer
  • Proteins
  • Rna Stability

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