Background: Liver cancer is a life threating disease as it is the fifth most common cancer and the
third most common cause of death worldwide with no safe, efficient, and economic drug available for treatment.
Methods: This study intended to investigate glycyrrhizin and its derivatives for possible use as a cytotoxic agent
and as a drug for liver cancer treatment. Thus, after treatment of liver cancer cell line HepG-2 with 50 μM of
each compound, cell viability was determined.
Results: The cytotoxicity assay showed glycyrrhizin derivatives ME-GA (18β-Glycyrrhetinic-30-methyl ester)
and AKBA (3-acetyl-11- keto-β-Boswellic acid) to be the most potent drug against liver cancer cell line HepG-2
with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 μM, respectively. Both the compounds showed higher 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 which might be attributed to its higher activity
and selectivity. Both ME-GA and AKBA contributed to inhibit cancer cell migration in the wound healing
assay and impeded colony formation. The use of flow cytometry to carry out cell cycle analysis and the determination
of possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M
that led to the inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its
ability to increase p53 transactivation.
Conclusion: This work highlights the cytotoxicity of glycyrrhizin and its derivatives 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.