Journal
CANCER LETTERS
Volume 346, Issue 2, Pages 206-216Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.01.016
Keywords
Oleanolic acid; Synthetic triterpenoids; CDDO; Pentacyclic triterpenoids; Inflammation cancer
Categories
Funding
- Singapore Ministry of Health's National Medical Research Council
- Singapore Ministry of Education [MOE2012-T2-2-139]
- Academic Research Fund [R-184-000-228-112]
- Cancer Science Institute of Singapore, Experimental Therapeutics I Program [R-713-001-011-271]
- National Cancer Institute/National Institutes of Health [R03CA136014]
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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.
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