Arachidonate Metabolism in Breast Cancer Cultures: Identification of Antagonists/Agonist for Possible Intervention Strategies.
Annual rept. 1 Oct 94-30 Sep 95,
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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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 cyclooxygenaseCO vs lipoxygenaseLO 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
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