A label free chemoproteomic-based platform to disclose cannabidiol molecular mechanism of action on chronic myelogenous leukemia cancer cells
Sara Ceccacci,
Lorenzo Corsi,
Lucio Spinelli,
Clarissa Caroli,
Matilde Marani,
Lisa Anceschi,
Matteo Mozzicafreddo,
Federica Pellati,
Maria Chiara Monti
Affiliations
Sara Ceccacci
Department of Pharmacy, Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy; PhD Program in Drug Discovery and Development, Department of Pharmacy, Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy
Lorenzo Corsi
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103/287, 41125, Modena, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy
Lucio Spinelli
Department of Pharmacy, Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy; Department of Pharmacy, Università degli Studi di Napoli ‘Federico II’, Via Domenico Montesano, 49, 80131, Napoli, Italy
Clarissa Caroli
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103/287, 41125, Modena, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy
Matilde Marani
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103/287, 41125, Modena, Italy
Lisa Anceschi
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103/287, 41125, Modena, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Via Campi 287, 41125, Modena, Italy
Matteo Mozzicafreddo
Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60126, Ancona, Italy
Federica Pellati
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103/287, 41125, Modena, Italy
Maria Chiara Monti
Department of Pharmacy, Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy; Corresponding author.
The discovery of the interactome of cannabidiol (CBD), a non-psychoactive cannabinoid from Cannabis sativa L., has been here performed on chronic myelogenous leukemia cancer cells, using an optimized chemo-proteomic stage, which links Drug Affinity Responsive Target Stability with Limited Proteolysis Multiple Reaction Monitoring approaches. The obtained results showed the ability of CBD to target simultaneously some potential protein partners, corroborating its well-known poly-pharmacology activity. In human chronic myelogenous leukemia K562 cancer cells, the most fascinating protein partner was identified as the 116 kDa U5 small nuclear ribonucleoprotein element called EFTUD2, which fits with the spliceosome complex. The binding mode of this oncogenic protein with CBD was clarified using mass spectrometry-based and in silico analysis.
