Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors
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Animals
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects*
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Benzamides / pharmacology
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Farnesyltranstransferase / antagonists & inhibitors
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Hodgkin Disease / drug therapy
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Hodgkin Disease / pathology*
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Humans
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K562 Cells / drug effects
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Methionine / analogs & derivatives
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Methionine / pharmacology
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Mice
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Neoplasm Transplantation
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Protein Prenylation / drug effects
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Protein Processing, Post-Translational / drug effects*
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Simvastatin / pharmacology*
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Simvastatin / therapeutic use
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Tumor Cells, Cultured / drug effects
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Benzamides
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Enzyme Inhibitors
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FTI 277
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GGTI 298
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Methionine
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Simvastatin
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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Farnesyltranstransferase