Lovastatin interacts with natural products to influence cultured hepatocarcinoma cell (hep-g2) growth.

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.