Inhibitory effect of pentalenolactone on vascular smooth muscle cell proliferation.

The effect of pentalenolactone, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, on rat vascular smooth muscle cell proliferation was studied. Addition of pentalenolactone together with serum to quiescent cells dose-dependently inhibited cell proliferation and DNA synthesis. This inhibition was not associated with cell death. When quiescent cells were stimulated with serum and then treated with pentalenolactone, the inhibitory effect on the DNA synthesis declined gradually. A similar result was obtained when PD 98059 (2'-amino-3'-methoxyflavone), an inhibitor of extracellular signal-regulated kinase1/2 (ERK1/2) kinase (MEK1/2), was added to the cells after serum stimulation. Pentalenolactone inhibited serum or protein kinase C activator (phorbol 12,13-dibutyrate)-induced phosphorylation of ERK1/2 and MEK1/2. In contrast, pentalenolactone had little effect on platelet-derived growth factor receptor autophosphorylation. Taken together, these results indicate that pentalenolactone inhibits vascular smooth muscle cell proliferation, and that this inhibition appears to be mediated by inhibition of the ERK1/2 cascade.