A Low Dose of Pure Cannabidiol Is Sufficient to Stimulate the Cytotoxic Function of CIK Cells without Exerting the Downstream Mediators in Pancreatic Cancer Cells

International Journal of Molecular Sciences

Amit Sharma¹  Ingo G. H. Schmidt-Wolf¹  Francesca Garofano¹  Maria A. Gonzalez-Carmona²  Hinrich Abken³ 

[1] Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital Bonn, 53127 Bonn, Germany;Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany;RCI Regensburg Center for Interventional Immunology, Department Genetic Immunotherapy, University Hospital Regensburg, 93053 Regensburg, Germany;

关键词: cytokine-induced killer cells;    cannabidiol;    pancreatic cancer;   

DOI  :  10.3390/ijms23073783

来源: DOAJ

【 摘 要 】

Despite numerous studies conducted over the past decade, the exact role of the cannabinoid system in cancer development remains unclear. Though research has focused on two cannabinoid receptors (CB1, CB2) activated by most cannabinoids, CB2 holds greater attention due to its expression in cells of the immune system. In particular, cytokine-induced killer cells (CIKs), which are pivotal cytotoxic immunological effector cells, express a high-level of CB2 receptors. Herein, we sought to investigate whether inducing CIK cells with cannabidiol can enhance their cytotoxicity and if there are any possible counter effects in its downstream cascade of phosphorylated p38 and CREB using a pancreatic ductal adenocarcinoma cell line (PANC-1). Our results showed that IL-2 modulates primarily the expression of the CB2 receptor on CIK cells used during ex vivo CIK expansion. The autophagosomal-associated scaffold protein p62 was found to co-localize with CB2 receptors in CIK cells and the PANC-1 cell line. CIK cells showed a low level of intracellular phospho-p38 and, when stimulated with cannabidiol (CBD), a donor specific variability in phospho-CREB. CBD significantly decreases the viability of PANC-1 cells presumably by increasing the cytotoxicity of CIK cells. Taken together, in our preclinical in vitro study, we propose that a low effective dose of CBD is sufficient to stimulate the cytotoxic function of CIK without exerting any associated mediator. Thus, the combinatorial approach of non-psychoactive CBD and CIK cells appears to be safe and can be considered for a clinical perspective in pancreatic cancer.

【 授权许可】

Unknown