Phyto- and Endo-Cannabinoids in Glioblastoma: Preliminary Antitumoral Evidence

Introduction: Glioblastoma is the most malignant and aggressive form of brain tumor and displays high rates of recurrence despite chemotherapy, and radiation. Numerous studies have shown pronounced cytotoxic effects of phytocannabinoids (mainly cannabidiol, CBD, and Δ9- tetrahydrocannabinol, THC) in glioblastoma in cell lines and animal models. The endocannabinoid system is an endogenous neuromodulatory network composed of endogenous cannabinoids (ECs), cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of ECs. ECs modulate inflammation and energy metabolism. They are dysregulated in glioblastoma. However, phytocannabinoids and ECs role in Glioblastoma has not yet been investigated. Objective: Investigate phytocannabinoids and ECs derivates in regulating glioblastoma cell lines growth. Materials and methods: CT-2A and GL-261 mouse glioblastoma cell lines were treated with different phytocannabinoids and ECs. Cytotoxicity was evaluated by MTT and cytofluorimetric analysis. Correlation between phytocannabinoids and endocannabinoid system was investigated by RT-PCR. Results: Phytocannabinoids and ECs reduced the growth of glioblastoma cell lines. Phytocannabinoids influenced the expression of endocannabinoids system genes. Conclusion: Different phytocannabinoids are effective in Glioblastoma growth. Dysregulation of endocannabinoid system in glioblastoma should be restored by phytocannabinoids.