Abstract
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.
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