Extra Virgin Olive Oil Phenols induce authophagy and apoptosis in human bladder cancer cell lines depending on tumor progression

Epidemiological evidences indicate that there is an inverse association between olive oil intake and bladder cancer risk and several data suggest that a key role to support these beneficial effects is played by its phenolic fraction. Bladder cancer is one of the most common cancers in Western countries. In particular, the transitional cell carcinoma histotype shows an aggressive behavior and the current therapies are ineffective. The anti-proliferative effects of an Extra Virgin Olive Oil phenolic Extract (EVOOE) has been investigated on RT112 and J82, two human bladder cancer cell lines employed as models of superficial and invasive bladder cancer, respectively.
EVOOE reduces cell viability in both cell lines triggering different processes. In RT112 cells, EVOOE triggers a non-protective autophagic response, evidenced by vacuoles formation and LC-3 lipidation (45%) causing a delay in cell growth (132microg/ml induces 30% reduction). Instead, in J82, the invasive transitional cell carcinoma, EVOOE treatment induces a rapid and remarkable decrease of cell viability (33 microg/ml for 24 h induces 40% reduction) triggering an apoptotic process, evidenced with Annexin V positivity and the increased activity of caspases 3 and 9. EVOOE exerts an antioxidant activity in both cell lines reducing ROS (30% in J82 and 15% in RT112) and increasing GSH level (20% in J82 and 40% in RT112). However, comparing the effects of EVOOE with those of other well-known antioxidants, the absence of correlation between antioxidant effects and reduced cell viability was evidenced. Moreover, using an inhibitor of GSH synthesis, we demonstrated that EVOOE acts independently from GSH modulation.
Data presented show that EVOOE possesses pleiotropic activities that intercept different pathways resulting in anti-proliferative effects independently of its antioxidant property