The GLP-1 Receptor Agonist Liraglutide Promotes Anticancer Activities in MCF7 Breast and PC-3 Prostate Cancer Cells by Modulating Glycolysis, Oxidative Stress and Adipokines

This research explored the Anticancer activities of the glucagon-like peptide-1 receptor agonist (GLP1Ra) liraglutide using MCF7 breast and PC-3 prostate Cancer cell lines. The study focused on key molecular pathways related to glycolysis and oxidative stress alongside adipokine profiles. The expression of GLP1R and its downstream signalling components (cAMP and PKA) was quantified in untreated and treated cells. Alterations in cell cycle and cell Apoptosis were evaluated by a flow cytometer. Expression of oncogenic (CCND1, CCND3, BCL2, Survivin) and tumour suppressor (p21, p27, Bax, Caspase-3) proteins, the PI3KAkt/mTOR axis and glycolytic regulators (HIF-α, LDHA, PDHK1, PDH) was examined by Western blot analysis. Adipokine concentrations (Adiponectin, Leptin, resistin), pro-oxidants (ROS/RNS, MDA, protein carbonyls) and Antioxidants (GSH, CAT) were assessed using ELISA. Liraglutide treatment led to pronounced upregulation of GLP1R expression and activation of cAMP/PKA signalling in both Cancer cell lines. Antiproliferative effects were evident through induced Apoptosis and cell cycle arrest alongside inhibition of CCND1, CCND3, BCL2 and Survivin with increased p21, p27, Bax and Caspase-3 expression. The PI3K/Akt/mTOR pathway was suppressed, while its negative regulators, PTEN and AMPKα, were upregulated. Liraglutide also shifted metabolic activity towards Oxidative Phosphorylation by suppressing HIF-α, LDHA and PDHK1, whereas PDH levels increased. Additionally, liraglutide raised Adiponectin levels while reducing Leptin and resistin. Oxidative stress markers increased substantially, accompanied by a decrease in antioxidant levels in both cell lines. Liraglutide induced Anticancer effects in breast and prostate Cancer cells, possibly by promoting Oxidative Phosphorylation, modulating adipokines and inducing oxidative stress-mediated Apoptosis.

PI3K/AKT/mTOR pathway; Warburg effect; adiponectin; leptin; resistin.