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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2008

Open Access 01-12-2008 | Research

TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma

Authors: Adrien Daigeler, Christina Brenzel, Daniel Bulut, Anne Geisler, Christoph Hilgert, Marcus Lehnhardt, Hans U Steinau, Annegret Flier, Lars Steinstraesser, Ludger Klein-Hitpass, Ulrich Mittelkötter, Waldemar Uhl, Ansgar M Chromik

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2008

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Abstract

Background

Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD), two substances with apoptogenic properties on human fibrosarcoma (HT1080).

Methods

Viability, apoptosis and necrosis were visualized by TUNEL-Assay and quantitated by FACS analysis (Propidiumiodide/AnnexinV staining). Gene expression was analysed by RNA-Microarray and the results validated for selected genes by rtPCR. Protein level changes were documented by Western Blot analysis. NFKB activity was analysed by ELISA and proliferation assays (BrdU) were performed.

Results and discussion

The single substances TRAIL and TRD induced apoptotic cell death and decreased proliferation in HT1080 cells significantly. Gene expression of several genes related to apoptotic pathways (TRAIL: ARHGDIA, NFKBIA, TNFAIP3; TRD: HSPA1A/B, NFKBIA, GADD45A, SGK, JUN, MAP3K14) was changed. The combination of TRD and TRAIL significantly increased apoptotic cell death compared to the single substances and lead to expression changes in a variety of genes (HSPA1A/B, NFKBIA, PPP1R15A, GADD45A, AXL, SGK, DUSP1, JUN, IRF1, MYC, BAG5, BIRC3). NFKB activity assay revealed an antipodal regulation of the several subunits of NFKB by TRD and TRD+TRAIL compared to TRAIL alone.

Conclusion

TRD and TRAIL are effective to induce apoptosis and decrease proliferation in human fibrosarcoma. A variety of genes seems to be involved, pointing to the NFKB pathway as key regulator in TRD/TRAIL-mediated apoptosis.
Appendix
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Metadata
Title
TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma
Authors
Adrien Daigeler
Christina Brenzel
Daniel Bulut
Anne Geisler
Christoph Hilgert
Marcus Lehnhardt
Hans U Steinau
Annegret Flier
Lars Steinstraesser
Ludger Klein-Hitpass
Ulrich Mittelkötter
Waldemar Uhl
Ansgar M Chromik
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2008
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-27-82

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