Accession Number:

ADB274459

Title:

Discovery of New Drugs That Target Peroxisomal Proliferator-Activated Receptor Gamma (PPAR-Gamma) for the Treatment of Breast Tumors

Descriptive Note:

Final rept. 1 Sep 2000-31 Aug 2001

Corporate Author:

MISSISSIPPI STATE UNIV MISSISSIPPI STATE

Personal Author(s):

Report Date:

2001-09-01

Pagination or Media Count:

28.0

Abstract:

The major goal of this project is to discover novel chemotherapeutic agents that act on a newly discovered molecular target in breast tumor cells. Recent studies have demonstrated that substances that activate the nuclear hormone receptortranscription factor, Peroxisome Proliferator-Activated Receptors-gamma PPAR-gamma can inhibit growth, cause terminal differentiation, and induce apoptosis in human breast tumor cells. In vitro molecular mechanism-targeted pharmacological assays were developed and used to discover small drug-like PPAR-gamma activators from chemically-rich marine organisms. Chemically unique marine oxylipins structurally novel lipoxygenase metabolites of marine fatty acids were shown to act as PPAR-gamma ligands, transactivate PPAR-gamma gene expression, induce cellular arrest, and cause cell death in MCF-7 breast tumor cells in vitro. Most currently know PPAR-gamma activators are fatty acid metabolites or structurally related to the synthetic thiazoilidinedione TZD class of insulin sensitizers. This research has discovered that cyanobacteria and marine algae produce natural products, found nowhere else in nature, that activate PPAR-gamma. These structurally unique marine natural products are chemically unrelated to any other class of known PPAR-gamma activators. It is envisioned that these novel chemical prototypes can be used as chemical ideas to design new antitumor agents that function through the activation of PPAR-gamma.

Descriptors:

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE


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