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.


CONCLUSIONS
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.
Popovich
David G
DG
Department of Chemistry, National University of Singapore, Science Drive 4, Singapore. chmpdg@nus.edu.sg
Tiaras
Felicia
F
Yeo
Chia Rou
CR
Zhang
Wei
W
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002211:Capsaicin / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008148:Lovastatin / Q000494:pharmacology / Q000627:therapeutic use*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D002392:Catechin; D008148:Lovastatin; C045651:epigallocatechin gallate; D003474:Curcumin; D002211:Capsaicin