Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Oleanolic acid (OA, 3 beta-hydroxyolean-12-en-28-oic acid) is a ubiquitous pentacyclic multifunctional tri-terpenoid, widely found in several dietary and medicinal plants. Natural and synthetic OA derivatives can modulate multiple signaling pathways including nuclear factor-kappa B, AKT, signal transducer and activator of transcription 3, mammalian target of rapamycin, caspases, intercellular adhesion molecule 1, vascular endothelial growth factor, and poly (ADP-ribose) polymerase in a variety of tumor cells. Importantly, synthetic derivative of OA, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), and its C-28 methyl ester (CDDO-Me) and C28 imidazole (CDDO-Im) have demonstrated potent antiangiogenic and antitumor activities in rodent cancer models. These agents are presently under evaluation in phase I studies in cancer patients. This review summarizes the diverse molecular targets of OA and its derivatives and also provides clear evidence on their promising potential in preclinical and clinical situations. (C) 2014 Elsevier Ireland Ltd. All rights reserved.