CBD Reverts the Mesenchymal Invasive Phenotype of Breast Cancer Cells Induced by the Inflammatory Cytokine IL-1?.

ABSTRACT: Cannabidiol (CBD) has been used to treat a variety of cancers and inflammatory conditions with controversial results. In previous work, we have shown that breast cancer MCF-7 cells, selected by their response to inflammatory IL-1? cytokine, acquire a malignant phenotype (6D cells) through an epithelial-mesenchymal transition (EMT). We evaluated CBD as a potential inhibitor of this transition and inducer of reversion to a non-invasive phenotype. It decreased 6D cell viability, downregulating expression of receptor CB1. The CBD blocked migration and progression of the IL-1?-induced signaling pathway IL-1?/IL-1RI/?-catenin, the driver of EMT. Cannabidiol reestablished the epithelial organization lost by dispersion of the cells and re-localized E-cadherin and ?-catenin at the adherens junctions. It also prevented ?-catenin nuclear translocation and decreased over-expression of genes for ?Np63?, BIRC3, and ID1 proteins, induced by IL-1? for acquisition of malignant features. Cannabidiol inhibited the protein kinase B (AKT) activation, a crucial effector in the IL-1?/IL-1RI/?-catenin pathway, indicating that at this point there is crosstalk between IL-1? and CBD signaling which results in phenotype reversion. Our 6D cell system allowed step-by-step analysis of the phenotype transition and better understanding of mechanisms by which CBD blocks and reverts the effects of inflammatory IL-1? in the EMT.

SUBMITTER: Garcia-Morales L 

PROVIDER: S-EPMC7177247 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature