176 | Preliminary observations on cannabinoid receptor activation in an in vitro steatosis model and in triple-negative breast cancer cells

Roberta Oliveri¹, Gianluca Lavanco², Giovanni Pratelli¹, Diana Di Liberto¹, Fabiana Plescia³, Anna De Blasio³, Francesca Vaccaro², Stella Cascioferro³, Flavia Zingales¹, Marianna Lauricella¹, Rosaria Maria Pipitone², Stefania Grimaudo², Fulvio Plescia², Daniela Carlisi¹ | ¹Department of Biomedicine, Neurosciences and Advanced Diagnostics BiND, University of Palermo, Italy; ²Department of Health Promotion Sciences, Maternal and Child Care, Internal Medicine and Medical Specialties “Giuseppe D'Alessandro”, University of Palermo, Italy; ³Department of Biological, Chemical and Pharmaceutical Sciences and Technologies STEBICEF - University of Palermo, Italy.

The endocannabinoid system is involved in the regulation of metabolism and cell survival, with effects that may vary depending on cellular context. In this work, we report preliminary data on the modulation of cannabinoid receptor signaling in an in vitro model of hepatic steatosis and in breast cancer cell lines, a tumor in which lipid metabolism is involved in chemoresistance. Steatosis was induced in HepG2 cells using a mixture of oleic and palmitic acids. Cells were treated with a cannabinoid receptor agonist CP55,940, a reference antagonist/inverse agonist AM251, and QD13, currently characterized as an antagonist with inverse agonist properties. In parallel, the triple-negative breast cancer cell lines MDA-MB-231 and BT-20 were treated under the same pharmacological conditions, in the absence of steatogenic medium. Cell viability was assessed by MTT assay, while intracellular neutral lipid accumulation was evaluated by Oil Red O staining. In steatotic HepG2 cells, cannabinoid receptor modulation was associated with changes in intracellular neutral lipid accumulation, as evidenced by Oil Red O staining. This effect was dependent on dose variations of CP55,940. In breast cancer cell lines, treatment with the cannabinoid receptor agonist resulted in a marked reduction in cell viability and was accompanied by evident morphological changes, whereas antagonist or inverse agonist treatments did not elicit comparable effects. Overall, these preliminary observations indicate that cannabinoid receptor modulation elicits divergent cellular responses in metabolic and tumor models, influencing lipid accumulation in hepatocytes and cell viability in breast cancer cells. Further studies will be required to elucidate the biochemical mechanisms underlying these effects and to define the contribution of cannabinoid receptor signaling in each cellular context.