Volltext-Downloads (blau) und Frontdoor-Views (grau)

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells

  • Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern. Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes. Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

Download full text files

Export metadata

Additional Services

Search Google Scholar Check availability

Statistics

Show usage statistics
Metadaten
Document Type:Article
Language:English
Author:Yutao Li, Amit Sharma, Michèle J. Hoffmann, Dirk Skowasch, Markus Essler, Hans Weiher, Ingo G. H. Schmidt-Wolf
Parent Title (English):Frontiers in Immunology
Volume:15
Article Number:1268652
Number of pages:17
ISSN:1664-3224
URN:urn:nbn:de:hbz:1044-opus-80708
DOI:https://doi.org/10.3389/fimmu.2024.1268652
PMID:https://pubmed.ncbi.nlm.nih.gov/38558822
Publisher:Frontiers Media
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2024/03/14
Copyright:© 2024 Li, Sharma, Hoffmann, Skowasch, Essler, Weiher and Schmidt-Wolf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Funding:The CIO Aachen Bonn Köln Düsseldorf is kindly supported by the Deutsche Krebshilfe (grant No. 70113470). In addition, we would like to thank the Microscopy Core Facility of the Medical Faculty at the University of Bonn for providing support and instrumentation funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Projektnummer 388169927.
Keyword:DNA double- strand breaks; DNA methylation; cannabidiol, immunotherapy; cytokine-induced killer cells; immunotherapy; long interspersed nuclear element-1; transient receptor potential vanilloid Type 2
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2024/03/21
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International