Inhibition of cell growth by lovastatin

Lovastatin has been shown to be a potent inhibitor of smooth muscle cell (SMC) growth (Liao et al., 2002; Mattingly et al., 2002). The drug is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. By inhibiting mevalonate (MVA) synthesis, lovastatin prevents the synthesis of isoprenoid intermediates which serve as lipid attachments for post-translational modification of various cell signalling proteins (Munro et al., 1994). Ras and Rho B proteins are major substrates for post-translational modification by isoprenylation. Since they regulate cell growth, studies have suggested lovastatin inhibits DNA synthesis and SMC growth by inhibiting isoprenylation of key signalling proteins (Raiteri et al., 1997). The aim of our study was to find out if the inhibition of SMC growth by lovastatin is caused by inhibition of HMG-CoA and could therefore be reversed by MVA.