Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology
Abstract
Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge preclinical evidence with future clinical application. We delineate the pleiotropic mechanisms by which OC modulates cancer hallmarks, including lysosomal membrane permeabilization (LMP)-mediated apoptosis, the inhibition of key oncogenic signaling pathways (c-MET/STAT3, PAR-2/TNF-α, COX-2/mPGES-1), the suppression of epithelial-to-mesenchymal transition (EMT), angiogenesis, and metabolic reprogramming. Furthermore, this review uniquely highlights the emerging role of OC in modulating drug resistance mechanisms by downregulating efflux transporters and sensitizing tumors to chemotherapy, targeted therapies, and immunotherapies. We also examine OC's bidirectional interaction with gut microbiota, underscoring its systemic immunometabolic effects. A major unmet need addressed by this review is the lack of consolidated knowledge regarding OC's pharmacokinetic limitations and drug-drug…
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