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.
BACKGROUND: Synthetic oleanolic acidtriterpenoid2-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 humanprostate 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.
Authors: Vitali Alexeev; Elizabeth Lash; April Aguillard; Laura Corsini; Avi Bitterman; Keith Ward; Adam P Dicker; Alban Linnenbach; Ulrich Rodeck Journal: Mol Cancer Ther Date: 2014-11-14 Impact factor: 6.261
Authors: Xiaohua Gao; Dorrah Deeb; Jiang Hao; Yongbo Liu; Ali S Arbab; Scott A Dulchavsky; Subhash C Gautam Journal: Anticancer Res Date: 2010-03 Impact factor: 2.480
Authors: Dorrah Deeb; Xiaohua Gao; Hao Jiang; Branislava Janic; Ali S Arbab; Yon Rojanasakul; Scott A Dulchavsky; Subhash C Gautam Journal: Biochem Pharmacol Date: 2009-09-24 Impact factor: 5.858