Abstract
(-)-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.
Highlights
Olive oil has been consumed by humans for millennia and is frequently associated with health-related properties
A randomized trial found that women who adhered to a Mediterranean diet supplemented with extra virgin olive oil (EVOO) had 62% less invasive breast cancer incidence than a control group that was advised to restrict dietary fats [5]
We treated a panel of cancer cells and normal human cells with 20 μM oleocanthal, and as expected, saw a sharp loss in viability within 24 hours among the cancer cells (MDA-MB-231 human breast cancer cells, PC3 human prostate cancer cell lines, and N134 murine pancreatic neuroendocrine tumors (PNET) cancer cells) while the non-cancerous cells (MCF10A human breast epithelial cells, HEK293T human kidney cells and BJ-hTERT human fibroblast cells) were less affected by oleocanthal treatment (p
Summary
Olive oil has been consumed by humans for millennia and is frequently associated with health-related properties. A meta analyses of nineteen observational studies performed between 1990 and 2011 that included approximately 35,000 individuals found that olive oil intake is inversely related to cancer prevalence [4]. A randomized trial found that women who adhered to a Mediterranean diet supplemented with extra virgin olive oil (EVOO) had 62% less invasive breast cancer incidence than a control group that was advised to restrict dietary fats [5]. These studies, did not distinguish between the protective effects of EVOO’s triglycerides and its phenolic components. To the best of our knowledge, no controlled study tested the effect of high phenolic EVOO on cancer
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