Established and novel NF-κB inhibitors lead to downregulation of TLR3 and the proliferation and cytokine secretion in HNSCC

Christian Meyer, Ralph Pries, Barbara Wollenberg*

*Korrespondierende/r Autor/-in für diese Arbeit
12 Zitate (Scopus)

Abstract

The transcriptional activation of NF-κB signalling has been identified as a major pathway involved in inflammation and tumor aggressiveness in a number of human cancers. Here we identify the impact of miscellaneous known and so far unknown NF-κB inhibitors originating from different drug classes on the function and proliferation of HNSCC. In detail: HNSCC cell lines were exposed to Acetylsalicylic Acid (ASA), Celecoxib, Dexamethasone, Curcumin and EPs 7630. Our major interest was to detect upstream alterations in cell signalling after applying NF-κB inhibiting substances. The inhibition of NF-κB signalling leads to an upstream regulation of Toll-like-receptor 3 (TLR3), a predominant receptor driving cell expansion. We find a marked downregulation of TLR3 and IKK complex, documenting upstream responses to NF-κB inhibition by every agent tested. In a second step we further analyse proliferation, cytokine production and alterations in the expression of downstream proteins such as cyclin D1 and c-Myc. Our data demonstrate decreased proliferation in response to incubation with aforementioned agents. Modulation of TLR3 and NF-κB expression is accompanied by altered profiles of IL-6 and IL-8 which are relevant cytokines in HNSCC progression. Proto-oncogenes cyclin D1 and c-myc are downregulated by all substances. Apart from the interplay of cytokines and TLR3, we substantiated EPs 7630 as a new and natural NF-κB inhibitor.

OriginalspracheEnglisch
ZeitschriftOral Oncology
Jahrgang47
Ausgabenummer9
Seiten (von - bis)818-826
Seitenumfang9
ISSN1368-8375
DOIs
PublikationsstatusVeröffentlicht - 01.09.2011

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