Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

Abstract

Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5 adenosine monophosphate-activated protein kinase, extracellular signal-regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice

“…As alveolar bone loss was high in the buccal region, we analyzed bone formation levels in the buccal region of the tooth root socket. To enhance the quality of bone formation, we evaluated the effect of OAA, which is an important therapeutic compound commonly used as an anticancer and anti‐inflammatory agent . Drug repositioning has been successfully used in recent years, owing to its advantages over de novo drug discovery and development .…”

“…To enhance the quality of bone formation, we evaluated the effect of OAA, which is an important therapeutic compound commonly used as an anticancer and anti-inflammatory agent. 14,16 Drug repositioning has been successfully used in recent years, owing to its advantages over de novo drug discovery and development. 32 This process saves time and money, as drugs approved for a disease may be tested for efficacy against other types of disorders.…”

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

“…Figure illustrates some examples: olive fruit and leaf contain high amounts of OA, after which the compound was named . OA is abundant in apple skin, papaya fruit, persimmon fruit and leaf, plum and loquat . OA is also found in soya beans, filamentous fungi and sedum aizoon .…”

“…Oleanane‐type triterpenoids, OA and OA derivatives exhibit many beneficial effects; notably, antioxidant, anti‐inflammatory effects and antidiabetic effects against type 2 diabetes mellitus . OA and its derivatives are not only effective in inhibiting malignant cell growth in vitro, but also effective against tumour growth in tumour‐bearing mice, such as breast cancer, hepatocellular carcinoma, colon cancer and leukaemia . CDDO analogues are in clinical trials as chemoprevention and chemotherapy drugs …”

“…12,13 OA and its derivatives are not only effective in inhibiting malignant cell growth in vitro, but also effective against tumour growth in tumour-bearing mice, such as breast cancer, hepatocellular carcinoma, colon cancer and leukaemia. 5,14 CDDO analogues are in clinical trials as chemoprevention and chemotherapy drugs. 10,15 One of the most notable pharmacological effects of OA and OA derivatives is generalized hepatoprotection.…”