RT Journal Article
SR Electronic
T1 Mevastatin-induced Apoptosis and Growth Suppression in U266 Myeloma Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1817
OP 1822
VO 24
IS 3A
A1 JUDIT JANOSI
A1 ANNA SEBESTYÉN
A1 JOZSEF BOCSI
A1 GABOR BARNA
A1 KATALIN NAGY
A1 ISTVAN VALYI-NAGY
A1 LASZLO KOPPER
YR 2004
UL http://ar.iiarjournals.org/content/24/3A/1817.abstract
AB Statins have been used successfully in the treatment of hypercholesterinaemia. 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 the mitochondrial membrane. Expression of Bcl-2 mRNA and protein was down-regulated, with no change in Bax or Bcl-XL protein production. The mitochondrial program was supported by caspase-8 and cleaved-Bid activity. None of the antibodies neutralizing the death-ligand/death-receptor pathway -TRAIL-R2Fc, anti-TNF-α, anti- FASL(NOK-1)- influenced the mevastatin-induced apoptosis. Mevastatin also stimulated shedding of syndecan-1 from the surface of myeloma cells. The apoptosis inducing effect of mevastatin could be considered as a potential participant in a complex antitumor protocol. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved