Lovastatin interacts with natural products to influence cultured hepatocarcinoma cell (Hep-G2) growth

Abstract

Objective: To assess the interaction of the hydroxy-3-methylglutaryl- coezyme A reductase inhibitor lovastatin individually and in combination with 3 natural plant compounds on hepatocarcinoma cell growth. Methods: The cytotoxic effects of lovastatin in combination with epigallocatechin gallate (EGCG), capsaicin, and curcumin were investigated in cultured hepatocarcinoma cells (Hep-G2), and the interactions were depicted using an isobolographical analysis. Results: All compounds tested reduced Hep-G2 cell growth to various degrees. In terms of individual cytotoxicity LC50 values, curcumin (55.5 ± 7.6 μmol/L) was found to be the most cytotoxic and had the lowest LC50, followed by lovastatin (62.3 ± 5.34 μmol/L), EGCG (82.1 ± 15.1 μmol/L), and capsaicin (199.5 ± 11.72 μmol/L). The individual LC50 values were used in a fix-fraction isobolographical analysis to predict the effect of combining lovastatin and the individual compounds. Experimentally derived LC50 values of 5 fractions containing fixed proportions of lovastatin to each of the 3 natural compounds allowed comparison of the experimentally derived LC50 to the predicted values depicted on the isobologram. Conclusion: Lovastatin in combination with capsaicin was found to be synergistic at all concentrations tested, and EGCG combinations produced both synergistic and additive results. Unexpectedly, lovastatin in combination with curcumin produced an antagonistic effect on cell growth, resulting in a greater concentration required than if the compounds were used individually.