New Triterpenoids for Prevention of Breast Cancer
Abstract
We have shown that the synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) is a highly potent inhibitor of the proliferation of several ER-positive and ER-negative human breast cancer cell lines. Furthermore, CDDO at nanomolar levels will block de novo synthesis of two inflammatory enzymes that have been implicated in the carcinogenic process, namely inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2). During the period of funding of this grant, we have attempted to use CDDO in vivo to prevent experimental breast cancer in rats, but we have not been successful thus far, in spite of the extremely high potency of CDDO as a suppressor of the growth of numerous breast cancer cells in culture. We attribute this poor activity in vivo to inadequate pharmacokinetic properties, so therefore we have undertaken the synthesis of a large number of derivatives of CDDO, which are esters, amides, and imidazolides, relatively easily made from CDDO itself. We have evaluated many of these new structures in cell culture; they are highly active as suppressors of synthesis of iNOS and as inhibitors of growth of many tumor cells in culture, including human breast cancer cells. Evaluation of these new agents in vivo is a future goal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA410760
Entities
People
- Michael B. Sporn
Organizations
- Dartmouth College