RETRACTED ARTICLE: Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures
Open Access
- 14 February 2020
- journal article
- retracted article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-17
- https://doi.org/10.1038/s41598-020-59468-4
Abstract
Radiotherapy combined with chemotherapy is the major treatment modality for human glioblastoma multiforme (GBM). GBMs eventually relapse after treatment and the average survival of GBM patients is less than two years. There is some evidence that cannabidiol (CBD) can induce cell death and increases the radiosensitivity of GBM by enhancing apoptosis. Beside initiation of death, CBD has been demonstrated as an inducer of autophagy. In the present study, we address the question whether CBD simultaneously induces a protective effect in GBM by upregulating autophagy. Addition of chloroquine that suppressed autophagic flux to 2D GBM cultures increased CBD-induced cell death, presenting proof for the protective autophagy. Blockage of autophagy upregulated radiation-induced cytotoxicity but only modestly affected the levels of cell death in CBD- or CBD/γ-irradiated 3D GBM cultures. Furthermore, CBD enhanced the pro-apoptotic activities of JNK1/2 and MAPK p38 signaling cascades while partially downregulated the pro-survival PI3K-AKT cascade, thereby changing a balance between cell death and survival. Suppression of JNK activation partially reduced CBD-induced cell death in 3D GBM cultures. In contrast, co-treatment of CBD-targeted cells with inhibitors of PI3K-AKT-NF-κB, IKK-NF-κB or JAK2-STAT3 pathways killed surviving GBM cells in both 2D and 3D cultures, potentially improving the therapeutic ratio of GBM.This publication has 75 references indexed in Scilit:
- JNK-signaling: A multiplexing hub in programmed cell deathGenes & Cancer, 2017
- Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells.2015
- The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma ModelMolecular Cancer Therapeutics, 2014
- Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC).Apoptosis, 2014
- The convergence of radiation and immunogenic cell death signaling pathwaysFrontiers in Oncology, 2012
- STATs in cancer inflammation and immunity: a leading role for STAT3Nature Reviews Cancer, 2009
- Differential Recovery of Neural Stem Cells in the Subventricular Zone and Dentate Gyrus After Ionizing RadiationThe International Journal of Cell Cloning, 2009
- Adding Chloroquine to Conventional Treatment for Glioblastoma MultiformeAnnals of Internal Medicine, 2006
- Hypothesis: cannabinoid therapy for the treatment of gliomas?Neuropharmacology, 2004
- The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1Cell, 1988