Dataset Information

Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties.

ABSTRACT:

Background

The transcription factor NF-κB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma [GBM]). Precise therapeutic modulation of NF-κB activity can suppress central oncogenic signaling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive.

Methods

In a pharmacogenomics study with a panel of transgenic glioma cells, we observed that NF-κB can be converted into a tumor suppressor by the non-psychotropic cannabinoid cannabidiol (CBD). Subsequently, we investigated the anti-tumor effects of CBD, which is used as an anticonvulsive drug (Epidiolex) in pediatric neurology, in a larger set of human primary GBM stem-like cells (hGSC). For this study, we performed pharmacological assays, gene expression profiling, biochemical, and cell-biological experiments. We validated our findings using orthotopic in vivo models and bioinformatics analysis of human GBM datasets.

Results

We found that CBD promotes DNA binding of the NF-κB subunit RELA and simultaneously prevents RELA phosphorylation on serine-311, a key residue that permits genetic transactivation. Strikingly, sustained DNA binding by RELA-lacking phospho-serine 311 was found to mediate hGSC cytotoxicity. Widespread sensitivity to CBD was observed in a cohort of hGSC defined by low levels of reactive oxygen species (ROS), while high ROS content in other tumors blocked CBD-induced hGSC death. Consequently, ROS levels served as a predictive biomarker for CBD-sensitive tumors.

Conclusions

This evidence demonstrates how a clinically approved drug can convert NF-κB into a tumor suppressor and suggests a promising repurposing option for GBM therapy.

SUBMITTER: Volmar MNM

PROVIDER: S-EPMC8563328 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties.

Volmar Marie N M MNM Cheng Jiying J Alenezi Haitham H Richter Sven S Haug Alisha A Hassan Zonera Z Goldberg Maria M Li Yuping Y Hou Mengzhuo M Herold-Mende Christel C Maire Cecile L CL Lamszus Katrin K Flüh Charlotte C Held-Feindt Janka J Gargiulo Gaetano G Topping Geoffrey J GJ Schilling Franz F Saur Dieter D Schneider Günter G Synowitz Michael M Schick Joel A JA Kälin Roland E RE Glass Rainer R

Neuro-oncology 20211101 11

<h4>Background</h4>The transcription factor NF-κB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma [GBM]). Precise therapeutic modulation of NF-κB activity can suppress central oncogenic signaling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive.<h4>Methods</h4>In a pharmacogenomics study with a panel of transgenic glioma cells, we observed that NF-κB can be converted into a tumor suppressor by the non-psych ...[more]

PMID: 33864076

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Dataset Information

Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties.

Background

Methods

Results

Conclusions

Publications

Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties.

Similar Datasets

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