Cannabinoids such as ajulemic acid (AJA), a synthetic derivative of THC-11-oic acid, and cannabidiol (CBD), a natural compound found in the <i>Cannabis</i> plant, are compounds that show promising results for the treatment of Ewing’s Sarcoma (ES), a pediatric bone cancer with a low survival rate. Cannabinoids would be ideal drugs because they have been shown to relieve pain and inflammation and induce apoptosis in ES cell lines without controversial psychoactive effects. While there is a lot of promise with cannabinoids as treatment for ES, the biochemical pathways affected in tumor cells are still widely unknown. PARP1, a protein expressed in ES cells that functions in DNA repair, is a promising target for the drug. In order to test the interactions between the drugs and PARP1, a docking suite within SYBYL-X-2.1.1, a computational program from Tripos Inc, will be used to dock cannabinoids to the ligand-binding domain of PARP1. The results will show how well binding occurs between these compounds, as well as where the binding should occur. These results can be compared with docking of known PARP1 inhibitors to discover whether or not they are binding to the protein in a similar way. An ELISA will be used to investigate the presence of cleaved PARP1 in cannabinoid-treated ES cells in order to elucidate the potential mechanism of cannabinoids for apoptosis. We hypothesize that cannabinoids will bind to PARP1 in a similar manner to known PARP1 inhibitors, and that these compounds will cleave PARP1 in ES cells.

Analysis of PARP1 interactions with cannabinoids

251st National Meeting (2016)

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