Figure 4

Reversal of statin-mediated inhibition of cytotoxicity by geranylgeranyl pyrophosphate. The natural killer cell cytotoxicity assay was used to determine whether statin-mediated inhibition of cytotoxicity could be reversed by intermediates of the mevalonate pathway. YT-INDY was incubated with lovastatin (12.5 µM) in the presence or absence of geranylgeranyl pyrophosphate (GGPP) (10 µM), dimethylallyl pyrophosphate (DMPP) (10 µM), farnesyl pyrophosphate (FPP) (10 µM), isopentenyl pyrophosphate (IPP) (10 µM) or squalene (200 µM) for 24 hours. YT-INDY treated with the solvent in which each statin was dissolved, served as controls. Each experiment was performed three times and the data was analyzed for statistical significance by Student’s t-test. Panel A demonstrates that only geranylgeranyl pyrophosphate could reverse the lovastatin-mediated inhibition of cytotoxicity. Panel B indicates that geranylgeranyl pyrophosphate could reverse the abrogation of cytotoxicity caused by five different statins.