Modulation of the endocannabinoid system reduces inflammatory signalling in canine mammary carcinoma cells

Background: Canine mammary carcinoma (CMC) is characterised by a chronic inflammatory microenvironment resembling human breast cancer; however, the upstream regulatory mechanisms driving this phenotype remain unclear. The endocannabinoid system (ECS) has emerged as a potential modulator of inflammation and tumour biology. This study investigated the role of the ECS in CMC and evaluated the anti-inflammatory effects of cannabidiol (CBD). Methods: of CBD (32 µM), and sub-cytotoxic concentrations (3, 10 and 20 µM) were subsequently applied for 24 h. Results: Canine mammary carcinoma-derived cells exhibited significant overexpression of ECS receptors (CB1, CB2, TRPV1, GPR55 and PPAR-α) compared to normal controls. These cells also showed increased secretion of pro-inflammatory cytokines, including IL-6, IL-8, TNF-α and IL-17A. Treatment with CBD at 10-20 µM significantly downregulated key inflammatory genes, particularly COX-2, IL-6 and TNF-α, and reduced corresponding cytokine release without compromising cell viability. Conclusion: The ECS is upregulated in CMC and appears to contribute to the inflammatory tumour microenvironment. Cannabidiol effectively attenuates this inflammatory phenotype at sub-cytotoxic concentrations, supporting its potential as a therapeutic agent in CMC.