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.


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.


CONCLUSIONS
These studies provide a rationale for clinical evaluation of CDDO-Me as adjuvant therapy for treatment of advanced and fatal form of prostate cancer.
Deeb
Dorrah
D
Department of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
Gao
Xiaohua
X
Dulchavsky
Scott A
SA
Gautam
Subhash C
SC
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
D017304:Annexin A5; C494811:BCL2L1 protein, human; D004792:Enzyme Precursors; D007527:Isoenzymes; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051020:bcl-X Protein; D009828:Oleanolic Acid; D045304:Cytochromes c; C445068:bardoxolone methyl; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate