Breast Cancer Prevention with a Novel Oleanane Triterpenoid: Preclinical Evidence and Anti-inflammatory Mechanisms

Breast cancer represents the second leading cause of death in women in the United States and chemoprevention may reverse the devastating impact of this disease. We have developed a novel synthetic oleanane triterpenoid (methyl-25-hydroxy-3-oxoolean-12-en-28-oate, methyl-amoorain or AMR-Me) and investigated its inhibitory effect and anti-inflammatory mechanisms against 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis which mimics human breast cancer. Oral administration of AMR-Me dose-dependently suppressed the incidence and burden of DMBA-initiated mammary tumors. AMR-Me downregulated the expression of intratumor cyclooxygenase-2, suppressed the degradation of inhibitory κB-α, and reduced the translocation of nuclear factor-κB (NF-κB) from cytosol to nucleus. The results of the present study provide the first experimental evidence that AMR-Me exerts a striking chemopreventive effect against DMBA-evoked mammary carcinogenesis in vivo by anti-inflammatory effects mediated through suppression of activated NF-κB signaling. This study may facilitate the clinical development of AMR-Me for the prevention and treatment of breast cancer which is an incurable disease.

This research was supported by the NIH/NCI grant R03CA136014.