Cannabigerol in vitro effect on Human Pancreatic Ductal Adenocarcinoma

Introduction Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic cancer. The five years survival is about 5% and the poor prognosis is correlated to the absence of specific symptoms, preventive diagnosis biomarkers, great invasiveness and treatment resistance. New strategies to treat this tumour are necessary. Cannabinoids, compounds derived from Cannabis sativa, showed promising results in several cancer models, but only few data are available regarding the anticancer effect of cannabigerol (CBG). In this work, it was investigated the in vitro effect of CBG on two human PDAC cell lines. Material and Methods CBG cytotoxicity on two PDAC cell lines was evaluated by MTT assay. The type of cell death induced by CBG was evaluated by Annexin V-FITC/PI staining and cytofluorimetric analysis and confirmed by the evaluation of Caspase-3 protein expression and activation by western blot. The modulation of genes involved in cancer cell aggressiveness was evaluated by western blot and by Milliplex assay. Modulation of autophagy was evaluated with western blot and acridine orange dye. The cytotoxicity of the combination of CBG and chemotherapeutic drugs was evaluated by MTT assay and the synergism was calculated with SynergyFinder. Results and Discussions CBG is cytotoxic on PDAC cell lines in a dose dependent manner and it induces apoptotic cell death. CBG modulates EGFR/Akt/mTOR and RAS pathways, involved in cancer cell aggressiveness, and induces autophagy in PDAC cell lines. Moreover, CBG potentiates the cytotoxic effect of gemcitabine and paclitaxel, the main chemotherapeutic drugs used in PDAC therapy, showing a synergistic effect with them. Conclusion Data show that CBG displays anticancer effects in vitro on PDAC cell lines, inducing cell death, interfering with many pathways involved in cancer progression and aggressiveness, and synergizing with chemotherapeutic drugs.