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Cell Commun Signal. 2011 May 24;9:15. doi: 10.1186/1478-811X-9-15.

LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells.

Author information

  • 1Karlsruher Institute of Technology, Institute of Toxicology and Genetics, PO-Box 3640, 76021 Karlsruhe, Germany. christine.blattner@kit.edu.

Abstract

BACKGROUND:

The incidence of cancer in patients with neurological diseases, who have been treated with LiCl, is below average. LiCl is a well-established inhibitor of Glycogen synthase kinase-3, a kinase that controls several cellular processes, among which is the degradation of the tumour suppressor protein p53. We therefore wondered whether LiCl induces p53-dependent cell death in cancer cell lines and experimental tumours.

RESULTS:

Here we show that LiCl induces apoptosis of tumour cells both in vitro and in vivo. Cell death was accompanied by cleavage of PARP and Caspases-3, -8 and -10. LiCl-induced cell death was not dependent on p53, but was augmented by its presence. Treatment of tumour cells with LiCl strongly increased TNF-α and FasL expression. Inhibition of TNF-α induction using siRNA or inhibition of FasL binding to its receptor by the Nok-1 antibody potently reduced LiCl-dependent cleavage of Caspase-3 and increased cell survival. Treatment of xenografted rats with LiCl strongly reduced tumour growth.

CONCLUSIONS:

Induction of cell death by LiCl supports the notion that GSK-3 may represent a promising target for cancer therapy. LiCl-induced cell death is largely independent of p53 and mediated by the release of TNF-α and FasL.Key words: LiCl, TNF-α, FasL, apoptosis, GSK-3, FasL.

PMID:
21609428
[PubMed]
PMCID:
PMC3115922
Free PMC Article
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