New Triterpenoids for Prevention of Breast Cancer
Annual rept. 1 Jun 1999-31 May 2000
DARTMOUTH COLL HANOVER NH
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We have recently shown that the synthetic triterpenoid, 2-cyano-3,12-dioxooiean-l,9,-dien- 28-dc acid CDDO is a highly patent inhibitor of the proliferation of several ER- positive and ER-negative human breast cancer cell lines. Furthermore, CDDO at nanomolar levels will block de nova synthesis of two inflammatory enzymes that have recently been implicated in the carcinogenic process, namely inducible nitric oxide synthase iNOS and inducible cyclooxygenase COX-2 . Current efforts are now underway to study whether chronic administration of CDDO can prevent the development of breast cancer in an animal model for this disease. Since we have shown in many other studies that combinations of chemopreventive agents are often more effective than single agents, we have also begun cell culture studies in both ER-positive and ER-negative breast cancer cells to explore the combined use of CDDO together with retinoids or ligands for the nuclear receptor, PPAR-gamma. If we find useful synergisms in cell culture, we will translate these results into suitable animal experiments for prevention of breast cancer in viva.
- Anatomy and Physiology
- Medicine and Medical Research