Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells.
Anticancer Res
; 35(11): 5827-37, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26504004
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Dronabinol
/
Canabidiol
/
Regulação Neoplásica da Expressão Gênica
/
Apoptose
/
Glioma
/
Proteínas de Choque Térmico
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article