Olive Oil Polyphenols in Cancer: Molecular Mechanisms and Therapeutic Promise

Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer activities in various experimental models. These compounds act synergistically through diverse mechanisms, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of cell proliferation, apoptosis, angiogenesis, and metastasis. Notably, oleocanthal selectively induces cancer cell death via lysosomal membrane permeabilization, while hydroxytyrosol and oleuropein exhibit potent radical-scavenging and anti-proliferative properties. This review synthesizes findings from in vitro, in vivo, and clinical studies on the anticancer potential of these polyphenols, with emphasis on their mechanisms of action and possible applications in cancer prevention and adjunctive therapy. Given the established link between obesity and cancer development, clinical studies examining the metabolic, anti-inflammatory, and immunomodulatory effects of olive polyphenols in populations with obesity or prediabetes provide valuable insights into their potential to influence cancer-related pathways indirectly. However, direct clinical evidence in cancer patients remains limited and preliminary, underscoring the need for focused, well-controlled trials with cancer-specific endpoints. Furthermore, it critically evaluates the translational relevance of these findings, highlighting gaps in clinical research and future directions. Literature was retrieved from Google Scholar, PubMed, and ScienceDirect using keywords such as cancer, immunomodulatory, anti-inflammatory, olive, tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal. Given the rising global cancer burden and the favorable safety profiles of these natural molecules, elucidating their molecular actions may support the development of novel integrative therapeutic strategies.