Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells

Judit Jánosi, Anna Sebestyén, József Bocsi, Gábor Barna, Katalin Nagy, István Vályi-Nagy, László Kopper

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1817-1822
Number of pages6
JournalAnticancer research
Volume24
Issue number3 A
Publication statusPublished - May 1 2004

Keywords

  • Apoptosis
  • Caspase
  • Mevastatin
  • Multiple myeloma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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