Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells

Cannabinoids possess a number of characteristics that make them putative anticancer drugs, and their value as such is currently being explored in a number of clinical studies. To further understand the roles that cannabinoids may have, we performed gene expression profiling in glioma cell lines cult...

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Bibliographic Details
Published in:Anticancer research 2015-11, Vol.35 (11), p.5827-5837
Main Authors: Scott, Katherine A, Dennis, Jayne L, Dalgleish, Angus G, Liu, Wai M
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Biomarkers, Tumor - genetics
Cannabidiol - pharmacology
Cell Proliferation - drug effects
Dronabinol - pharmacology
Drug Synergism
Gene Expression Profiling
Gene Expression Regulation, Neoplastic - drug effects
Glioma - drug therapy
Glioma - metabolism
Glioma - pathology
Hallucinogens - pharmacology
Heat-Shock Proteins - antagonists & inhibitors
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
Humans
Immunoenzyme Techniques
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Tumor Burden - drug effects
Tumor Cells, Cultured
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Summary:Cannabinoids possess a number of characteristics that make them putative anticancer drugs, and their value as such is currently being explored in a number of clinical studies. To further understand the roles that cannabinoids may have, we performed gene expression profiling in glioma cell lines cultured with cannabidiol (CBD) and/or Δ9-tetrahydrocannabinol (THC), and pursued targets identified by this screening. Results showed that a large number of genes belonging to the heat shock protein (HSP) super-family were up-regulated following treatment, specifically with CBD. Increases were observed both at the gene and protein levels and arose as a consequence of increased generation of ROS by CBD, and correlated with an increase in a number of HSP client proteins. Furthermore, increases impeded the cytotoxic effect of CBD; an effect that was improved by co-culture with pharmacalogical inhibitors of HSPs. Similarly, culturing glioma cells with CBD and HSP inhibitors increased radiosensitivity when compared to CBD-alone. Taken together, these data indicate that the cytotoxic effects of CBD can be diminished by HSPs that indirectly rise as a result of CBD use, and that the inclusion of HSP inhibitors in CBD treatment regimens can enhance the overall effect.
ISSN:1791-7530