LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells
<p>Abstract</p> <p>Background</p> <p>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,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-05-01
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| Series: | Cell Communication and Signaling |
| Online Access: | http://www.biosignaling.com/content/9/1/15 |
| _version_ | 1819043088002187264 |
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| author | Thiele Wilko Nazarenko Irina Marinescu Gabriela Kaufmann Larissa Oberle Carolin Sleeman Jonathan Blattner Christine |
| author_facet | Thiele Wilko Nazarenko Irina Marinescu Gabriela Kaufmann Larissa Oberle Carolin Sleeman Jonathan Blattner Christine |
| author_sort | Thiele Wilko |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Here we show that LiCl induces apoptosis of tumour cells both <it>in vitro </it>and <it>in vivo</it>. 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.</p> <p>Conclusions</p> <p>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.</p> <p>Key words: LiCl, TNF-α, FasL, apoptosis, GSK-3, FasL</p> |
| first_indexed | 2024-12-21T09:51:13Z |
| format | Article |
| id | doaj.art-f35e5b2fa07947dc912c28d1e1e43e29 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-21T09:51:13Z |
| publishDate | 2011-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-f35e5b2fa07947dc912c28d1e1e43e292022-12-21T19:08:11ZengBMCCell Communication and Signaling1478-811X2011-05-01911510.1186/1478-811X-9-15LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cellsThiele WilkoNazarenko IrinaMarinescu GabrielaKaufmann LarissaOberle CarolinSleeman JonathanBlattner Christine<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Here we show that LiCl induces apoptosis of tumour cells both <it>in vitro </it>and <it>in vivo</it>. 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.</p> <p>Conclusions</p> <p>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.</p> <p>Key words: LiCl, TNF-α, FasL, apoptosis, GSK-3, FasL</p>http://www.biosignaling.com/content/9/1/15 |
| spellingShingle | Thiele Wilko Nazarenko Irina Marinescu Gabriela Kaufmann Larissa Oberle Carolin Sleeman Jonathan Blattner Christine LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells Cell Communication and Signaling |
| title | LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells |
| title_full | LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells |
| title_fullStr | LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells |
| title_full_unstemmed | LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells |
| title_short | LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells |
| title_sort | licl induces tnf α and fasl production thereby stimulating apoptosis in cancer cells |
| url | http://www.biosignaling.com/content/9/1/15 |
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