Arachidonate Metabolism in Breast Cancer Cultures: Identification of Antagonists/Agonist for Possible Intervention Strategies.
Abstract
MCF-7 wild type (WT) cells have been examined for their sensitivity to various inhibitors of arachidonate metabolism as outlined in the proposal. One aim was to determine the effects of cyclooxygenase(CO) vs lipoxygenase(LO) inhibitors on proliferation in breast cancer cultures. Optimal suppression of proliferation was observed using inhibitors of 5-LO, platelet activating factor, and protein kinase C. CO inhibitors stimulated proliferation at conc. specific for PGH synthase-1. New drugs, heteropoly anions, free-radical scavengers which probably alter arachidonate metabolism, are quite effective antiproliferative agents. In order to see if these inhibitors have potential in chemotherapy, preliminary experiments have established their relative lack of toxicity in cultures of normal human bone marrow stroma cells. Certain of the heteropoly anions were not toxic in bone marrow cultures at concentrations showing effective antiproliferative activity in MCF-7 wT and multidrug-resistant (MDR) cells; these inhibitors did not readily induce development of MDR in WT cultures. Experiments have been done to establish quiescence in cultures; these cultures recover from quiescence to respond normally to signals. Quiescent cultures are being examined for agonist-stimulated arachidonate metabolism
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1995
- Accession Number
- ADB206345
Entities
People
- Marti Jett
Organizations
- Walter Reed Army Institute of Research