[Mevastatin induced apoptosis in U266 human myeloma cell line]

Magy Onkol. 2004;48(4):333-7. Epub 2005 Jan 17.
[Article in Hungarian]

Abstract

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.

Publication types

  • English Abstract

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lovastatin / analogs & derivatives*
  • Lovastatin / pharmacology*
  • Membrane Glycoproteins / drug effects
  • Multiple Myeloma / drug therapy*
  • Proteoglycans / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Syndecan-1
  • Syndecans
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2L1 protein, human
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Membrane Glycoproteins
  • Proteoglycans
  • Proto-Oncogene Proteins c-bcl-2
  • SDC1 protein, human
  • Syndecan-1
  • Syndecans
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • mevastatin
  • Lovastatin