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

Cell Communication and Signaling

Research

Larissa Kaufmann¹  Gabriela Marinescu¹  Carolin Oberle¹  Christine Blattner¹  Wilko Thiele²  Jonathan Sleeman²  Irina Nazarenko² 

[1] Karlsruher Institute of Technology, Institute of Toxicology and Genetics, PO-Box 3640, 76021, Karlsruhe, Germany;Karlsruher Institute of Technology, Institute of Toxicology and Genetics, PO-Box 3640, 76021, Karlsruhe, Germany;University of Heidelberg, Medical Faculty Mannheim, Ludolf-Krehl-Str. 13-17, 68167, Mannheim, Germany;

关键词: LiCl;    Proliferate Cell Nuclear Antigen;    HCT116 Cell;    U2OS Cell;    MT450 Cell;   

DOI  :  10.1186/1478-811X-9-15

 received in 2010-10-22, accepted in 2011-05-24,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsHere 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.ConclusionsInduction 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

【 授权许可】

Unknown   
© Kaufmann et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.