Synthetic Cannabinoid Activity Against Colorectal Cancer Cells.

Autor: Raup-Konsavage WM; Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania., Johnson M; Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania., Legare CA; Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania., Yochum GS; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania., Morgan DJ; Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.; Department of Anesthesiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania., Vrana KE; Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
Jazyk: angličtina
Zdroj: Cannabis and cannabinoid research [Cannabis Cannabinoid Res] 2018 Dec 21; Vol. 3 (1), pp. 272-281. Date of Electronic Publication: 2018 Dec 21 (Print Publication: 2018).
DOI: 10.1089/can.2018.0065
Abstrakt: Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new therapeutic strategies are still required. Here we screened a synthetic cannabinoid library to identify compounds that uniformly reduce the viability of seven CRC cell lines. Material and Methods: Seven distinct CRC cell lines were treated with 10 μM cannabinoid compounds (from a library of 370 molecules) for 48 h, and cell viability was subsequently measured with MTS assay. Dose-response curves were conducted for compounds that were found to reproducibly reduce cell viability of one or more cell lines. Results: We identified 10 compounds from the library that were able to reduce cell viability of CRC cell lines (with an IC 50 ≤ 30 μM). Of these compounds, seven were specific for CRC cells, and six were effective in all CRC cell lines tested. Treatment with traditional phytocannabinoids (THC or CBD) was either ineffective or much less potent and only partially efficacious. Treatment with antagonists for the known cannabinoid receptors (alone or in combination) failed to block the activity of the most potent of identified compounds. Conclusion: We identified three families of cannabinoid compounds that reduce CRC cell viability through a noncanonical receptor mechanism. Future modification of these compounds may lead to the development of novel therapies to treat this disease.
Competing Interests: The authors have no conflicts of interest, and no competing financial interests exist.
Databáze: MEDLINE
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