[Mevastatin induced apoptosis in U266 human myeloma cell line].
Statins have been used successfully in the treatment of hypercholesteremia. Moreover, in vitro studies have shown that statins can trigger apoptosis in a variety of tumor cell lines. In the present study we analysed the effect of mevastatin -- a novel inhibitor of HMG-COA reductase, the rate-limiting enzyme of the mevalonate pathway -- on U266 human myeloma cells. Apoptosis induced by mevastatin was associated with increased caspase activity and depolarisation of mitochondrial membrane. Expression of BCL-2 mRNA and protein was down-regulated, with no change in BAX or BCLxL protein production. The mitochondrial program was supported by caspase-8 and cleaved BID activity. None of the antibodies neutralising death-ligand/death-receptor pathway -- TRAIL-R2Fc, anti-TNF-a, anti FASL (NOK-1) -- influenced the mevastatin-induced apoptosis. Mevastatin also stimulated shedding of syndecan-1 from the surface of myeloma cells.
Jánosi
Judit
J
Országos Gyógyintézeti Központ, Budapest 1135, Hungary. janosijudit@hotmail.com
Sebestyén
Anna
A
Bocsi
József
J
Barna
Gábor
G
Nagy
Katalin
K
Vályi-Nagy
István
I
Kopper
László
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000187:drug effects; D009101:Multiple Myeloma / Q000188:drug therapy*; D011509:Proteoglycans / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1; D053667:Syndecans; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D019253:Proto-Oncogene Proteins c-bcl-2; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C012258:mevastatin; D008148:Lovastatin