“Colorectal cancer (CRC), found in the intestinal tract, is initiated and progresses through various mechanisms, including the dysregulation of signaling pathways. Several signaling pathways, such as EGFR and MAPK, involved in cell proliferation, migration, and apoptosis, are often dysregulated in CRC.
Although cannabidiol (CBD) has previously induced apoptosis and cell cycle arrest in vitro in CRC cell lines, its effects on signaling pathways have not yet been determined. An in silico analysis was used here to assess partner proteins that can bind to CBD, and docking simulations were used to predict precisely where CBD would bind to these selected proteins. A survey of the current literature was used to hypothesize the effect of CBD binding on such proteins.
The results predict that CBD could interact with EGFR, RAS/RAF isoforms, MEK1/2, and ERK1/2. The predicted CBD-induced inhibition might be due to CBD binding to the ATP binding site of the target proteins. This prevents the required phosphoryl transfer to activate substrate proteins and/or CBD binding to the DFG motif from taking place, thus reducing catalytic activity.”
https://pubmed.ncbi.nlm.nih.gov/39194723/
“This in silico study predicts that CBD could play a pivotal role in inhibiting the EGFR and MAPK pathways since almost all the proteins involved in this pathway interact with CBD. The most notable interactions occur between CBD and EGFR, KRAS, BRAF, and MEK1, as reflected by docking scores and being the most critically mutated or dysregulated proteins in colorectal cancer. CBD is proposed to act as an inhibitor of these proteins mainly by binding to the ATP catalytic binding site, which prevents phosphotransfer and the subsequent downstream activation of the substrate proteins. Secondly, CBD can act by binding to the DFG, which is adjacent to the hydrophobic pocket. The catalytic activity of this target protein is inhibited by this mechanism. Since the effect of CBD on these proteins has not yet been investigated, future studies should aim to determine if CBD indeed binds to these predicted target sites in these proteins and if the expected inhibitory effect occurs. Furthermore, in vitro phosphorylation studies on the selected proteins may determine if the phosphorylation of these proteins is affected by CBD treatment. In conclusion, CBD is predicted to interact with multiple role-players in the EGFR and MAPK pathways, potentially inhibiting these pathways and proteins.”