(-)-Oleocanthal and (-)-oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells

PLoS One. 2019 Aug 14;14(8):e0216024. doi: 10.1371/journal.pone.0216024. eCollection 2019.


(-)-Oleocanthal (oleocanthal) is a phenolic compound found in varying concentrations in extra virgin olive oil oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal, as well as naturally oleocanthal-rich extra virgin olive oils, induced damage to cancer cells' lysosomes leading to cellular toxicity in vitro and in vivo. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we found oleocanthal treatment reduced tumor burden and extended lifespan of mice engineered to develop pancreatic neuroendocrine tumors. Finally, following-up on numerous correlative studies demonstrating consumption of olive oil reduces cancer incidence and morbidity, we observed that extra virgin olive oils naturally rich in oleocanthal sharply reduced cancer cell viability and induced lysosomal membrane permeabilization while oleocanthal-poor oils did not. Our results are especially encouraging since tumor cells often have larger and more numerous lysosomes, making them especially vulnerable to lysosomotropic agents such as oleocanthal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes / administration & dosage*
  • Animals
  • Apoptosis
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Membrane Permeability / drug effects*
  • Cyclopentane Monoterpenes / administration & dosage*
  • Lysosomes / drug effects*
  • Lysosomes / metabolism
  • Mice
  • Necrosis
  • Neuroectodermal Tumors, Primitive / drug therapy*
  • Neuroectodermal Tumors, Primitive / pathology
  • Olive Oil / administration & dosage*
  • Phenols / administration & dosage*
  • Plant Oils / administration & dosage*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Aldehydes
  • Cyclopentane Monoterpenes
  • Olive Oil
  • Phenols
  • Plant Oils
  • oleocanthal