Cannabidiol Regulates CD47 Expression and Apoptosis in Jurkat Leukemic Cells Dependent upon VDAC-1 Oligomerization

TL;DR

Cannabidiol (CBD) reduces CD47 levels and causes cell death in leukemia cells through a process involving VDAC-1 protein clustering.

Contribution

This study reveals a novel mechanism by which CBD induces apoptosis in T-ALL cells via VDAC-1 oligomerization, independent of cannabinoid receptors.

Findings

CBD downregulates CD47 expression and induces apoptosis in Jurkat leukemic cells.

CBD's effects are rescued by a VDAC-1 oligomerization inhibitor but not by cannabinoid receptor modulators.

CBD also induces similar effects in primary human CD4+ T cells, albeit to a lesser extent.

Abstract

Background: Cannabidiol (CBD) is a major non-psychoactive phytocannabinoid that exerts multiple biological effects in the body. It has been shown to exert anti-cancer effects in a variety of cancer cells, including acute lymphoblastic leukemia of pre-T cell origin (T-ALL), a highly aggressive hematological malignancy. However, the mechanisms underlying CBD’s anti-cancer effects are not fully understood. Furthermore, cancer cells abundantly express surface CD47, which is a negative regulator of phagocytosis and linked with cell survival/death. Little is known about CBD effects on the expression of CD47 in T-ALL cells. The objectives of this study were to address these issues. Methods: Studies were conducted in vitro using Jurkat cells and human peripheral blood mononuclear cells in different culture conditions, CBD concentrations, and in the presence or absence of different reagents. Results: CBD downregulates CD47 expression and induces apoptosis in Jurkat cells. Similar biological effects of CBD were also observed in primary human CD4+ T cells, albeit at reduced levels. The CBD’s effects on CD47 expression and apoptosis were not rescued by a cannabinoid receptor (CBR)-2 agonist, a CBR-2 antagonist, or an anion channel blocker. However, these effects on CD47 expression and apoptosis were significantly rescued by a Voltage-Dependent Anion Channel (VDAC)-1 oligomerization inhibitor. Conclusions: Overall, we conclude that CBD downregulates CD47 expression and induces apoptosis involving VDAC-1 oligomerization. Furthermore, they also suggest that CBD’s pro-apoptotic effects on primary human T cells should also be monitored if it is used as an anti-cancer adjuvant or neo-adjuvant therapeutic in cancer patients.

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