ggti-298 and Hodgkin-Disease

Statins are used to treat hypercholesterolemia and seem to have a preventive effect against cancer through pleiotropic effects including prenylation-inhibition. So far nothing is known about the activity of statins or more specific prenylation-inhibitors in Hodgkin's lymphoma (HL). We, therefore, evaluated the anti-HL activity of simvastatin and specific prenylation-inhibitors. 2 microM Simvastatin induced caspase-related apoptosis via depletion of prenylation-substrates in several HL-cell lines. Furthermore, it effectively impaired tumor growth in a mouse model for HL. Since the prenylation-inhibitors FTI-277 and GGTI-298 were also effective against HL-cells, we conclude that statins and specific prenylation-inhibitors should be evaluated in HL patients.

Topics: Alkyl and Aryl Transferases; Animals; Antineoplastic Agents; Apoptosis; Benzamides; Enzyme Inhibitors; Farnesyltranstransferase; Hodgkin Disease; Humans; K562 Cells; Methionine; Mice; Neoplasm Transplantation; Protein Prenylation; Protein Processing, Post-Translational; Simvastatin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays