Effects of the non-psychoactive cannabinoid cannabidiol on human glioblastoma cells

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive cancers in adult humans and long-term survival rates are very low. Standard treatments remain mostly unsuccessful, for which reason new therapies are currently studied. These include immunotherapies that stimulate the patient’s immune system to fight tumor cells effectively. Also, cannabinoids have been shown to possess a variety of antitumoral characteristics like the inhibition of tumor growth by inducing apoptosis. I have investigated the effects of a non-lethal dose of the non-psychoactive cannabinoid cannabidiol (CBD) on the expression of membrane-bound heat shock protein 70 (Hsp70) on human glioblastoma cells. I could show that the expression level of Hsp70 was not affected by a treatment with CBD; however, an increased percentage of tumor cells did express Hsp70 on the cell membrane. Furthermore I have analysed the cytotoxicity of lymphocytes towards the CBD-treated and untreated glioblastoma cells as Hsp70 acts as a target for natural killer (NK) cells. In contrast to a cytokine stimulation of the immune cells with IL-2 and the Hsp70- peptide TKD, the CBD-based treatment of GBM-cells did not show any positive effects on the cytolysis of the tumor cells by the lymphocytes. This leads to the conclusion that not the amount of Hsp70-membrane-positive tumor cells but rather the expression level per cell is relevant for the effectiveness of a lymphocyte-based therapy. In order to find optimized, targeted therapies for the treatment of glioblastoma, a further investigation of molecular mechanisms, in particular regarding the relation between tumor, immune system and modulating substances like cannabinoids is necessary.