Simvastatin-dependent apoptosis in Hodgkin's lymphoma cells and growth impairment of human Hodgkin's tumors in vivo.
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.
von Tresckow
Bastian
B
Laboratory of Immunotherapy, Clinic I of Internal Medicine, University Hospital Cologne, Cologne, Germany. bastian.von-tresckow@uk-koeln.de
von Strandmann
Elke Pogge
EP
Sasse
Stephanie
S
Tawadros
Samir
S
Engert
Andreas
A
Hansen
Hinrich P
HP
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006689:Hodgkin Disease / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009368:Neoplasm Transplantation; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; C096856:FTI 277; C102521:GGTI 298; D008715:Methionine; D019821:Simvastatin; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase