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.
Highlights
Cancer is known as one of the major global health problems throughout the world, mainly due to changes in lifestyle, as well as unhealthy diets and environmental pollution [1]
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
This study suggested that oleanolic acid can cause apoptosis through mitochondrial-related pathways promoting the release of mitochondrial-associated caspases and pro-apoptotic Bax proteins [91]
Summary
Cancer is known as one of the major global health problems throughout the world, mainly due to changes in lifestyle, as well as unhealthy diets and environmental pollution [1]. The researchers that are in favor of the “whole” argue that the therapeutic efficacy of an extract is the outcome of synergistic or additive effects of its various bioactive components, while those who prefer purified compounds contend that, unlike isolated compounds, several phytochemicals present as a mixture in a natural source are not bioavailable, or have limited bioavailability and, are less useful. Both arguments present valid hypotheses and, despite the fact that a significant amount of investigation has been carried out in the field, results do not proclaim a winning side [2,11]. This review presents the chemistry, sources, and bioavailability, as well as the anticancer effects of oleanolic acid, with a particular emphasis on molecular mechanisms of action
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