Development of Novel Bifunctional Compounds That Induce Apoptosis in Prostate Cancer Cells

Abstract

We have designed and synthesized a novel compound (11?) that efficiently triggers apoptosis in prostate cancer cells such as LNCaP. This bifunctional compound was designed to form DNA adducts that are camouflaged by the androgen receptor making them less readily repaired in AR+ prostate cancer cells. The aims of our studies are to investigate the mechanisms by which 11? is able to trigger apoptosis in target cells. Methods have been developed that permit us to determine the fates of 11?-DNA adducts in treated cells in culture as well as in tumors growing in animal models. Another objective is to identify the signaling events that lead from DNA adducts to activation of the apoptotic program. Finally we have obtained encouraging results from animal experiments that indicate that molecules such as 11? may have clinical potential for the treatment of human tumors.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2009
Accession Number
ADA502889

Entities

People

  • John M. Essigmann
  • Robert G. Croy

Organizations

  • Massachusetts Institute of Technology

Tags

DTIC Thesaurus Topics

  • Alcohols
  • Androgen Receptors
  • Androgens
  • Apoptosis
  • Chemical Synthesis
  • Chemistry
  • Diseases And Disorders
  • Electrospray Ionization
  • Liquid Chromatography
  • Mass Spectrometry
  • Medical Personnel
  • Molecules
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Spectrometry
  • Tissues

Fields of Study

  • Chemistry

Readers

  • Geochemistry
  • Prostate Cancer Biology.
  • Systems Analysis and Design