Liver cancer is a life threating disease as it occupies the fifth most common cancers from incidences and the third cause of death worldwide and with no available safe, efficient, economic drug for treatment.Therefore, this study intended to investigate different glycyrrhizin and their derivatives for possible use as a cytotoxic agent and as a possible drug for liver cancer treatment. Thus, after treatment against liver cancer cell line HepG-2 with 50 µM of each compounds cell viability was determined.The cytotoxicity assay showed that glycyrrhizin derivative ME-GA (18β-Glycyrrhetinic-30-methyl ester) and AKBA (3-acetyl-11- keto-β-Boswellic acid) were most potent against liver cancer cell line HepG-2 with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 µM, respectively. Both compounds showed superior selectivity towards hepatocellular carcinoma rather than the normal lung fibroblast cell line WI-38. The presence of methyl ester at C-30 greatly increased the cytotoxicity of ME-GA and may attribute for its superior activity and selectivity. Both ME-GA and AKBA contribute the ability to inhibit the cancer cell migration in the wound healing assay and inhibited colony formation. Using flow cytometry to determine cell cycle analysis and determination the possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that lead to inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation.This work highlights the cytotoxicity of glycyrrhizin and its derivative for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. The most cytotoxic compound was ME-GA (18β-Glycyrrhetinic-30-methyl ester) with no cytotoxic effect on the normal cell line. In summary this new derivative may be used as an alternative or complementary medicine for liver cancer.
