Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state.

Transformation of thyroid cells with either K-ras or H-ras viral oncogenes produces cell types with different phenotype and different response to the inhibition of the prenylation pathway by 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyltransferase inhibitors. These inhibitors induce apoptosis in K-ras-transformed FRTL-5 cells (FRTL-5-K-Ras) whereas cell cycle arrest is induced in H-ras-transformed FRTL-5 (FRTL-5-H-Ras). In FRTL-5-K-Ras cells, the product of K-ras gene is implicated in the scavenging of reactive oxygen species (ROS) through the activation of extracellular-signal-regulated kinase (ERK)1/2 kinases.

HMG-CoA reductase inhibitors inhibit rat propylthiouracil-induced goiter by modulating the ras-MAPK pathway.

The aim of this study was to evaluate in vivo the antiproliferative effect of an inhibitor of isoprenoids metabolism, lovastatin, in an experimental model of propylthiouracil-induced goiter. In thyroid cells, thyrotropin (TSH)-induced proliferation requires active isoprenoid synthesis, and the HMG-CoA reductase inhibitors have antiproliferative effects in vitro. Propylthiouracil treatment (PTU) of rats led to thyroid hypertrophy and hyperplasia by TSH-induced activation of the mitogen-activated protein kinase (MAPK) pathway.

N6-isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation.

The physiological effects of a variety of N6-substituted adenine and adenosine derivatives called cytokinins have been documented in plants, but information on their occurrence and function in other biological system is limited. Here we investigated the anti-proliferative effect of N6-isopentenyladenosine (i6A), an adenosine and isoprenoid derivative, in a thyroid cell system, FRTL-5 wild-type, and K-ras transformed KiMol cells. Addition of i6A to FRTL-5 cells caused a dose-dependent arrest of the G0-G1 cell phase transition associated with a reduction of cells in the S phase that was much more evident in KiMol cells.