PhD Graduate Seminar of Mor Cohen-Harel (Meiri Lab)
18/10/2022 13:00
Mor Cohen-Harel (Meiri Lab)

“The Antitumor Effects of Cannabinoids in Glioblastoma Multiforme”
Glioblastoma multiforme is an aggressive brain tumor whose current treatments are insufficient due to its high invasiveness and heterogeneity, rapid growth and acquired therapy resistance. There is a great need to develop therapeutics that overcome this resistance and improve the treatment. Some studies have shown that the major cannabinoids from the Cannabis plant, Δ9-tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD), can improve glioblastoma cell response to radiation and chemotherapy, and moreover, directly affect tumor growth and cell viability.
As our lab routinely characterizes over 140 phytocannabinoids that exist in cannabis extracts in addition to THC and CBD, this research focused on discovering phytocannabinoids with antitumor effects on glioblastoma and understanding their mechanism of action. We studied each extract’s properties, recognized the minimal effective concentration that induces cell death in glioblastoma and defined the most effective cannabis extract.
We examined the combination of this extract with Bortezomib (BTZ), a proteasome inhibitor currently used as a second-line treatment in glioblastoma, and demonstrated a stronger and more rapid apoptotic response, in an additive manner.
From this effective extract, we isolated and identified Cannabigerol (CBG) as the essential cannabinoid for inducing glioblastoma programmed cell death. CBG showed great potency also as a single treatment when used in a high dose. We found that CBG targets glioblastoma via the CB1 receptor of the endocannabinoid system. It’s signaling pathway involves a significant upregulation of the transcription factor EGR1, which leads to an increase in multiple downstream apoptotic markers and directs the cell to apoptosis. We were able to demonstrate that CBG works in a similar manner also in an in-vivo mice model. Therefore, we believe that CBG is a promising therapeutic candidate that may be used, alone or in a combination with BTZ, in the treatment of glioblastoma patients.