Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: preclinical and clinical evidence.
Oleanolic acid (OA, 3β-hydroxyolean-12-en-28-oic acid) is a ubiquitous pentacyclic multifunctional triterpenoid, widely found in several dietary and medicinal plants. Natural and synthetic OA derivatives can modulate multiple signaling pathways including nuclear factor-κB, 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.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Muthu K
MK
Shanmugam
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Xiaoyun
X
Dai
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore; School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia, Australia; Department of Biological Sciences, University of North Texas, Denton, TX, USA.
Alan Prem
AP
Kumar
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Benny K H
BK
Tan
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore. Electronic address: phcgs@nus.edu.sg.
Gautam
G
Sethi
Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA, USA. Electronic address: abishayee@auhs.edu.
Anupam
A
Bishayee
D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
D014315:Triterpenes; C450739:oleanonic acid
CDDO; Inflammation cancer; Oleanolic acid; Pentacyclic triterpenoids; Synthetic triterpenoids