18-β-Glycyrrhetinic acid encapsulated PLGA nanoparticles attenuate lung cancer proliferation and migration

Conventional treatment methods to treat lung cancer include radiation therapy, chemotherapy, and immunotherapy. However, they cause severe adverse effects and recurrence risk. 18-β-glycyrrhetinic acid (18-β-Gly), a naturally occurring bioactive compound extracted from the liquorice plant has demonstrated anticancer potential by suppressing cancer cell growth, angiogenesis, and metastasis. Although 18-β-Gly possesses potential therapeutic abilities, the application of 18-β-Gly into clinical practices is hindered due to its inferior physicochemical characteristics such as poor bioavailability and low water solubility. Poly lactic-co-glycolic acid (PLGA) is a synthetic polymer with great tuneable options for a nano-drug delivery system used for various diseases, including cancer. Formulating 18-β-Gly into PLGA has helped to overcome challenges imposed by the poor physicochemical characteristics of 18-β-Gly. For this research, 18-β-Gly-PLGA was tested for its anticancer ability using A549 human lung adenocarcinoma lines found in lung cancer. Findings showed that 18-β-Gly-PLGA has favourable physicochemical characteristics, such as sustained in vitro drug release and good entrapment efficiency. 18-β-Gly-PLGA was also able to inhibit 15% and 50% proliferation of A549 cells at 2.5 μM and 50 μM respectively and 28% inhibition of A549 cell migration at 5 μM concentration. Oncogenes such as KRT18, EGFR, BRAF and KRAS were significantly downregulated by 43%, 19.3%, 14.7% and 13.7% respectively as part of the anticancer effects and the underlying mechanism of 18-β-Gly-PLGA. Significant reduction in the expression of cancer proliferation and migration-associated proteins such as receptor tyrosine-protein kinase ErbB2, survivin, macrophage colony-stimulating factor and mesothelin was also observed. The findings of this study demonstrate the promising potential of 18-β-Gly-PLGA as a potential anticancer agent.