CDDO-me induces apoptosis and inhibits Akt, mTOR and NF-kappaB signaling proteins in prostate cancer cells.

BACKGROUND: Synthetic oleanolic acid triterpenoid 2-cyano-3,12-dioxooleana-, 9(11)-dien-28-oic acid (CDDO) and its methyl ester (CDDO-Me) and imidazole (CDDO-Im) derivatives exhibit potent antitumor activity against diverse types of tumor cell lines. However, the anticancer activity of these triterpenoids against prostate cancer cells has not been reported.

MATERIALS AND METHODS: The apoptosis-inducing activity of CDDO-Me in human prostate cancer cell lines was investigated using flow cytometry and immunoblotting.

RESULTS: Prostate cancer cells are highly sensitive to CDDO-Me at concentrations of 1.25 to 10 microM. The primary mode of tumor cell destruction was apoptosis as demonstrated by increase in annexin V-FITC binding, activation of procaspases, release of cytochrome c from mitochondria, and inhibition of anti-apoptotic proteins. Furthermore, CDDO-Me inhibited the levels of anti-apoptotic Akt, mTOR and NF-kappaB (p65) signaling molecules.

CONCLUSION: These studies provide a rationale for clinical evaluation of CDDO-Me as adjuvant therapy for treatment of advanced and fatal form of prostate cancer.