Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells

Judit Jánosi, A. Sebestyén, József Bocsi, G. Barna, Katalin Nagy, István Vályi-Nagy, L. Kópper

Research output: Contribution to journalArticle

20 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 2004

Fingerprint

Apoptosis
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Growth
bcl-X Protein
Syndecan-1
Mevalonic Acid
Death Domain Receptors
Caspase 8
Mitochondrial Membranes
Caspases
Neutralizing Antibodies
Tumor Cell Line
Oxidoreductases
mevastatin
Ligands
Messenger RNA
Enzymes
Proteins

Keywords

  • Apoptosis
  • Caspase
  • Mevastatin
  • Multiple myeloma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells. / Jánosi, Judit; Sebestyén, A.; Bocsi, József; Barna, G.; Nagy, Katalin; Vályi-Nagy, István; Kópper, L.

In: Anticancer Research, Vol. 24, No. 3 A, 05.2004, p. 1817-1822.

Research output: Contribution to journalArticle

Jánosi, J, Sebestyén, A, Bocsi, J, Barna, G, Nagy, K, Vályi-Nagy, I & Kópper, L 2004, 'Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells', Anticancer Research, vol. 24, no. 3 A, pp. 1817-1822.
Jánosi J, Sebestyén A, Bocsi J, Barna G, Nagy K, Vályi-Nagy I et al. Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells. Anticancer Research. 2004 May;24(3 A):1817-1822.
Jánosi, Judit ; Sebestyén, A. ; Bocsi, József ; Barna, G. ; Nagy, Katalin ; Vályi-Nagy, István ; Kópper, L. / Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells. In: Anticancer Research. 2004 ; Vol. 24, No. 3 A. pp. 1817-1822.
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