title: 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.
authors.affiliation: Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia. lovro.ziberna@mf.uni-lj.si.
authors.forename: Lovro
authors.initials: L
authors.lastname: Žiberna
authors.affiliation: Department of Molecular Biology, Institute Ruđer Bošković, Bijenička c. 54, 10000 Zagreb, Croatia. dsamec@irb.hr.
authors.forename: Dunja
authors.initials: D
authors.lastname: Šamec
authors.affiliation: Department of Pharmaceutical Botany, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hațieganu", Ghe. Marinescu 23, 400337 Cluj-Napoca, Romania. mocan.andrei@umfcluj.ro.|ICHAT and Institute for Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3-5, 400372 Cluj-Napoca, Romania. mocan.andrei@umfcluj.ro.
authors.forename: Andrei
authors.initials: A
authors.lastname: Mocan
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran. Nabavisf@gmail.com.
authors.forename: Seyed Fazel
authors.initials: SF
authors.lastname: Nabavi
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, 18301 N. Miami Avenue, Miami, FL 33169, USA. abishayee@ularkin.org.
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore 54000, Pakistan. ammadfarooqi@rlmclahore.com.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Research Group on Community Nutrition and Oxidative Stress and CIBEROBN (Physiopathology of Obesity and Nutrition), University of Balearic Islands, E-07122 Palma de Mallorca, Balearic Islands, Spain. tosugo@hotmail.com.
authors.forename: Antoni
authors.initials: A
authors.lastname: Sureda
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran. Nabavi208@gmail.com.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Nabavi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000072001:Diet, Healthy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D009828:Oleanolic Acid
keywords: anticancer effect; healthy diet; oleanolic acid; olive; signaling pathways