Effects of Glycyrrhetic Acid on Human Chronic Myelogenous Leukemia Cells

Objectives: Chronic myelogenous leukemia (CML) is a type of blood cancer that is initially treated with imatinib (first Abl kinase inhibitor). However, some patients with CML develop imatinib resistance. Several new generation drugs have been developed, but do not overcome this problem. Glycyrrhetic acid (GA) is a plant-derived pentacyclic triterpenoid that exhibits multiple pharmacological properties for the treatment of cancers. The current study aimed to investigate the effects of GA on the K562 cell line (Bcr-Abl positive leukemia).

Materials and methods: The MTT cell proliferation assay was employed to evaluate the cytotoxic effect of GA compared with imatinib (positive control) against leukemia and normal blood cells. For detection of cell death, an apoptotic/necrotic/healthy assay was performed against the K562 cell line. To investigate the kinase inhibitory activity of GA, the Abl1 kinase profiling assay and a molecular docking study were performed.

Results: GA showed Abl kinase inhibitory activity with an IC₅₀ value of 29.2 μM and induced apoptosis in the K562 cell line after 6 h of treatment.

Conclusion: The current findings indicate that this class of plant extract could be a potential candidate for treatment of CML.

Keywords: Abl kinase; K562 cells; Pentacyclic triterpenoid; apoptosis; glycyrrhetic acid.