CANNABINOIDS AS METABOLIC REPROGRAMING AGENTS IN PROSTATE CANCER CELLS

Cancer is characterized by uncontrolled proliferation of cells and invasion of neighboring tissues and spreading. As an additional hallmark, all type of cancers are linked to impaired mitochondrial function and energy metabolism supporting a view of cancer as primarily a metabolic disease. Cannabinoids have been reported to affect mitochondrial functions. We previously demonstrated that CBD (alone and in combination with CBG) reduced tumor progression in TRAMP mice, which uniformly and spontaneously develop multistage autochthonous (orthotopic) prostate tumors following the onset of puberty. We also demonstrated that the combination between [1:1/CBD:CBG] mix and Enzalutamide (MDV3100), a standard chemo used for metastatic castration-resistant prostate cancer, synergistically reduced the percentage of pathological adenomers and tumor progression from PIN towards well-differentiated cancer. Finally, we set up an in vivo model of hormone refractory prostate with TRAMP mice and we showed that the CBD/CBG mixture (1:1) significantly reduced tumor relapse and reestablished the sensitivity to MDV3100 in animals under hormone refractory status. Here, we investigate whether purified plant cannabinoids (CBD and CBG) affect respiration rates and mitochondrial function in an in vitro model (TRAMP-C2 cells) derived from TRAMP tumors as well as in a MDV3100-resistant phenotype of TRAMPC2 cells. Preliminary results indicate that CBD modulates mitochondria membrane potential in TRAMP-C2 cells by fluorescence imaging. The effect in MDV3100-resistant cells is currently under investigation. The effect of both phytocannabinoids (CBG and CBG) on different mitochondrial protein complex functions and membrane parameters will be measured by means of oxygen consumption and EPR spectroscopy.