Date of Degree

9-2019

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

David Foster

Committee Members

Jill Bargonetti-Chavarria

Diego Loayza

Ana Maria Cuervo

Nancy Du

Subject Categories

Cancer Biology | Cell Biology | Food Chemistry

Keywords

Oleocanthal, Olive Oil, EVOO, Cancer, Cell Death, Lysosomes

Abstract

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 induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. 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 more vulnerable to lysosomotropic agents such as oleocanthal.

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