Monthly Archives: September 2024

Mechanistic Insights into the Impact of WIN 55, 212-2, a Synthetic Cannabinoid, on Adhesion Molecules PECAM-1 and VE-cadherin in HeLa Cells: Implications on Cancer Processes

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“The endocannabinoid (eCB) system comprises endogenous ligands, cannabinoid receptors (CBRs) and proteins involved in their regulation; its alteration leads to many diseases including cancer. Thus, becomes a therapeutic target for synthetic cannabinoids aimed to control cancer cell proliferation, migration, adhesion and invasion. However, little is known about adhesion molecules regulation through CBRs activation.

Consequently, the aim of this study was to evaluate the effects of a CB1/CB2 agonist, WIN-55, 212-2 (WIN), on the regulation of adhesion molecules PECAM-1 and VE-cadherin in HeLa cells. CBRs expression was evaluated by immunofluorescence staining in HeLa cells. Cell viability by MTT, cell adhesion by crystal violet, adhesion molecules expression and location by Western blot and immunofluorescence staining assays were assessed on cells treated with different WIN concentrations.

Results show that CB1, CB2 and GPR55 receptors are expressed in HeLa cells. Additionally, biphasic effects were observed in their metabolic activity and adhesive properties: low WIN concentrations significantly increased them, in contrast, were decreased at high ones as compared to controls (p < 0.0001), demonstrating that WIN elicits opposite effects depending on the concentration and exposure time. PECAM-1 was detected in cytoplasm, membrane and perinuclear region of HeLa cells, whereas VE-cadherin had a nuclear distribution. There were not significant differences in PECAM-1 and VE-cadherin expression and location, suggesting that WIN does not modulate these proteins.

These findings support the potential use of WIN due to its anticancer properties without dysregulating adhesion molecules. WIN possible contribution to inhibit cancer progression should be further investigated.”

https://pubmed.ncbi.nlm.nih.gov/39228102/

https://www.tandfonline.com/doi/full/10.1080/15376516.2024.2399132

Cannabidiol enhances Atezolizumab efficacy by upregulating PD-L1 expression via the cGAS-STING pathway in triple-negative breast cancer cells

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“The treatment of patients with triple negative breast cancer (TNBC) relies on cytotoxic therapy. Currently, atezolizumab and chemotherapy can be combined in patients with TNBC. However, this approach is not effective for all patients with low reactivity to atezolizumab. As there is a lack of alternative treatment options, new anti-cancer drugs are urgently needed to enhance atezolizumab reactivity against TNBC. Recent strategies have focused on regulating the expression of programmed death-ligand 1 (PD-L1) or enhancing immune response activation by combining anti-cancer drugs with immune checkpoint inhibitors (ICIs).

Cannabidiol (CBD), a cannabinoid component derived from the cannabis plant, has been reported to have anti-cancer therapeutic potential because of its capacity to induce apoptotic cell death in tumor cells while avoiding cytotoxicity in normal cells.

Previous studies have demonstrated the effects of CBD on apoptosis in various cancer cell types. However, the potential role of CBD as an immune modulator in the regulation of PD-L1 expression and anti-cancer immune responses remains to be explored.

In this study, we found that CBD stimulated PD-L1 expression in TNBC cells, which significantly induced the CBD-mediated cGAS-STING pathway activation. Taken together, we demonstrated that the combination of CBD and anti-PD-L1 antibody enhances the anti-cancer immune response in vitro and in vivo experiments.

Our findings identified the mechanism of PD-L1 regulation by CBD in TNBC cells and suggested that CBD could be a potential candidate for the development of new combinatorial strategies with ICIs in TNBC patients.”

https://pubmed.ncbi.nlm.nih.gov/39226389/

https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-23-0902/747763/Cannabidiol-enhances-Atezolizumab-efficacy-by