New Approaches to Chemoprevention of Breast Cancer.
Final rept. 1 Sep 96-31 Aug 98,
DARTMOUTH COLL HANOVER NH
Pagination or Media Count:
Triterpenoids, natural products related to steroids and retinolds, represent an important class of new structures for drug discovery, with potential applications in many fields of medicine, particularly cancer. This project involves the development of new synthetic triterpenoids for eventual use as agents for chemoprevention or chemotherapy of breast cancer. Although the naturally occurring triterpenoids, ursolic acid UA and oleanolic acid OA, have been shown to have some anti-carcinogenic activity, they are relatively weak agents. During the past year, we have synthesized over 150 new triterpenoids, and many of these have been assayed as inhibitors of de novo formation of inducible nitric oxide synthase iNOS and inducible cyclooxygenase COX-2, two enzymes highly relevant to the carcinogenesis in the breast. We have also screened these new triterpenoids as inducers of differentiation in NB-4 leukemia cells and as non-cytotoxic suppressors of estrogen-stimulated growth in MCF-7 breast cancer cells. Several new triterpenoids are markedly more active in these assays than their respective parents, UA or OA.
- Medicine and Medical Research