Proteomic analysis of invasive breast cancer cells treated with CBD reveals new proteins associated with the reversal of their Epithelial-Mesenchymal Transition

Cannabidiol (CBD) has been used in the treatment of cancer types associated with an inflammatory microenvironment. Although it has been demonstrated that CBD blocks and reverses the epithelial-mesenchymal-transition (EMT) induced by IL-1β, there is limited understanding of how CBD regulates these processes. MCF-7 cells were used to obtain the aggressive phenotype called 6D cells, CBD was then applied to reverse the EMT, to restore a benign epithelial phenotype. In this work, the protein expression in cells going through these processes was analyzed by mass spectrometry. By comparing proteomes of 6D vs. MCF-7 cells, as well as the proteomes of 6D+CBD cells vs. 6D cells or MCF-7 cells, it was foud that GOLGA2, KRT16, and RPRD2 expression was up-regulated by IL-1β and subsequently down-regulated by CBD, and KLHDC7B protein was repressed by IL-1β, and induced by CBD. These observations suggest that these four proteins could represent points of crosstalk between the IL-1β and CBD signaling pathways. Additionally, two protein networks were predicted; one associated with EMT including the proteins BRCA1, MSN, and CORO1A; and other associated with the CBD signaling, consisting of proteins SUPT16H, SETD2, and H2BC12, suggesting that CBD restores the epithelial morphology epigenetically and highlights potential targets for anticancer therapy.