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一种基于无标记化学蛋白质组学的平台，用于揭示大麻二酚对慢性粒细胞白血病癌细胞的分子作用机制。

A label free chemoproteomic-based platform to disclose cannabidiol molecular mechanism of action on chronic myelogenous leukemia cancer cells.

作者信息

Ceccacci Sara, Corsi Lorenzo, Spinelli Lucio, Caroli Clarissa, Marani Matilde, Anceschi Lisa, Mozzicafreddo Matteo, Pellati Federica, Monti Maria Chiara

机构信息

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.

出版信息

Heliyon. 2024 Jan 5;10(1):e24196. doi: 10.1016/j.heliyon.2024.e24196. eCollection 2024 Jan 15.

DOI:10.1016/j.heliyon.2024.e24196
PMID:38268604
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10806336/
Abstract

The discovery of the interactome of cannabidiol (CBD), a non-psychoactive cannabinoid from 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 analysis.

摘要

本文利用优化的化学蛋白质组学平台，将药物亲和反应靶点稳定性与有限蛋白水解多重反应监测方法相结合，在慢性髓性白血病癌细胞上开展了对源自大麻的一种非精神活性大麻素——大麻二酚（CBD）相互作用组的研究。所得结果表明，CBD能够同时靶向一些潜在的蛋白质伴侣，证实了其广为人知的多药理学活性。在人慢性髓性白血病K562癌细胞中，最引人注目的蛋白质伴侣被鉴定为一种名为EFTUD2的116 kDa U5小核核糖核蛋白元件，它与剪接体复合物相关。利用基于质谱的方法和分析，阐明了这种致癌蛋白与CBD的结合模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/a501d6efe618/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/fedfd664ed9b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/079815a926b7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/ed99ad69d0fb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/45aed8e14e49/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/a501d6efe618/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/fedfd664ed9b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/079815a926b7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/ed99ad69d0fb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/45aed8e14e49/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de6c/10806336/a501d6efe618/mmcfigs1.jpg

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Phytother Res. 2022 Feb;36(2):914-927. doi: 10.1002/ptr.7357. Epub 2022 Feb 2.
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A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD).
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Basic Clin Pharmacol Toxicol. 2022 Apr;130(4):439-456. doi: 10.1111/bcpt.13710. Epub 2022 Feb 6.
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