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The protective effect of cannabinoids against colorectal cancer cachexia through modulation of inflammation and immune responses.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 May; Vol. 161, pp. 114467. Date of Electronic Publication: 2023 Mar 03. - Publication Year :
- 2023
-
Abstract
- Cancer cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, and there are currently no FDA-approved medications. In the present study, upregulation of six cytokines was observed in serum samples from patients with colorectal cancer (CRC) and in mouse models. A negative correlation between the levels of the six cytokines and body mass index in CRC patients was seen. Gene Ontology analysis revealed that these cytokines were involved in regulating T cell proliferation. The infiltration of CD8 <superscript>+</superscript> T cells was found to be associated with muscle atrophy in mice with CRC. Adoptive transfer of CD8 <superscript>+</superscript> T cells isolated from CRC mice resulted in muscle wasting in recipients. The Genotype-Tissue Expression database showed that negative correlations between the expression of cachexia markers and cannabinoid receptor 2 (CB2) in human skeletal muscle tissues. Pharmacological treatment with Δ <superscript>9</superscript> -tetrahydrocannabinol (Δ <superscript>9</superscript> -THC), a selective CB2 agonist or overexpression of CB2 attenuated CRC-associated muscle atrophy. In contrast, knockout of CB2 with a CRISPR/Cas9-based strategy or depletion of CD8 <superscript>+</superscript> T cells in CRC mice abolished the Δ <superscript>9</superscript> -THC-mediated effects. This study demonstrates that cannabinoids ameliorate CD8 <superscript>+</superscript> T cell infiltration in CRC-associated skeletal muscle atrophy via a CB2-mediated pathway. Serum levels of the six-cytokine signature might serve as a potential biomarker to detect the therapeutic effects of cannabinoids in CRC-associated cachexia.<br />Competing Interests: Conflict of interest statement The authors disclose no conflicts of interest.<br /> (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Humans
Mice
Animals
Dronabinol pharmacology
Dronabinol therapeutic use
Cachexia drug therapy
Cachexia etiology
Cachexia prevention & control
CD8-Positive T-Lymphocytes
Cytokines
Inflammation
Immunity
Muscular Atrophy
Cannabinoids pharmacology
Cannabinoids therapeutic use
Colorectal Neoplasms complications
Colorectal Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 161
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 36871538
- Full Text :
- https://doi.org/10.1016/j.biopha.2023.114467