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

Abstract

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.

Anticancer effect of SZC017, a novel derivative of oleanolic acid, on human gastric cancer cells

“…It also serves as an aglycone of triterpenoid saponins that is linked with sugar chains to form glycosides. Both OA and its derivatives possess several biological activities, including hepatoprotective effects, antioxidant, anti-inflammatory, antiviral and anticancer activities (2)(3)(4). Many OA derivatives have shown their chemopreventive and chemotherapeutic functions among a series of cancer types, such as acute myeloid leukemia, breast cancer and prostate cancer (5)(6)(7).…”

Bardoxolone Methyl Suppresses Hepatitis B Virus Large Surface Protein Variant W4P-Related Carcinogenesis and Hepatocellular Carcinoma Cell Proliferation Via the Inhibition of Signal Transducer and Activator of Transcription 3 Signaling

“…CDDO-me exerted potent anti-inflammatory and anti-cancer activities [16][17][18]. It effectively suppressed breast cancer, lung cancer, osteosarcoma, and melanoma [18]. Previous studies have shown that the anti-tumor activity of CDDO-me is largely due to NRF2 activation and NF-κB inhibition [19].…”

“…In attempts to develop synthetic triterpenoids with enhanced efficacy, bardoxolone methyl (CDDO-methyl ester; CDDO-me; RTA402) was developed based on the scaffold of oleanolic acid. CDDO-me exerted potent anti-inflammatory and anti-cancer activities [16][17][18]. It effectively suppressed breast cancer, lung cancer, osteosarcoma, and melanoma [18].…”

Oleanolic acid protects against diabetic cardiomyopathy via modulation of the nuclear factor erythroid 2 and insulin signaling pathways

“…OL widely exists in plants, such as white snake tongue grass, hawthorn fruit, clove, papaya, Ligustrum lucidum and Prunella vulgaris (11). Experimental studies have demonstrated that OL has effective liver and kidney protective properties, inhibits platelet aggregation and has hypolipidemic, hypoglycemic, anti-inflammatory, anti-cancer, anti-stress, anti-ulcer and anti-microbial properties (12,13). OL is used to treat acute jaundice, chronic poisoning hepatitis, liver fibrosis and cirrhosis (12).…”