A Potential Therapeutic Role of J Series Prostaglandins in PPARy Mediated Treatment of Breast Cancer
Abstract
The peroxisome proliferator activated receptor gamma (PPAR gamma), is a potential therapeutic target for the treatment of breast cancer but the endogenous ligand for PPAR gamma is not yet known. Recent data suggest that the endogenous ligand of PPAR gamma may be a bioactive metabolite of arachidonic acid that is synthesized in normal breast tissue. Activation of PPAR gamma with different agonists (e.g. l5deoxy delta l2,l4PGJ2, troglitazone) elicits different physiological responses in breast cancer cells (i.e. differentiation or apoptosis) raising questions of the role PPARy plays in normal breast cell physiology. Results from our initial experiments show that prostaglandin metabolites of arachidonic acid inhibit cell cycle progression of MDA-MB-231 breast cancer cells. This cell cycle block induces apoptosis of breast cancer cells and inhibits tumor formation in nude mice. We hypothesize that human breast cancer cell lines (and human breast cancer tumors) have aberrant PPAR gamma mediated signal transduction pathways or contain disrupted pathways for the metabolism of fatty acid derivatives that act as PPAR gamma agonists. Understanding the metabolism of fatty acids in breast cancer cells, and elucidating the molecular and signal transduction events that are mediated by PPARy agonists may lead to novel strategies for the prevention and treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA410054
Entities
People
- Arta M. Monjazeb
Organizations
- Wake Forest University