KINK-1, a Novel Small-Molecule Inhibitor of IKKβ, and the Susceptibility of Melanoma Cells to Antitumoral Treatment

Abstract

Inhibition of constitutive and induced IKKbeta-activity through treatment with KINK-1 might increase tumor susceptibility to chemotherapy.

Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations

“…In some experiments, lymphoma cells were pre-exposed for 30 min to the pharmacological NF-kB inhibitors Bay11-7082 (1 mM; an IkBa phosphorylation inhibitor; Sigma-Aldrich), TPCA-1 (0.5 mM; an IKK-2 inhibitor; Merck), or KINK-1 (0.4 mM; an IKK-2 inhibitor; kindly provided by M. Schmidt-Supprian [Schon et al 2008]) prior to a subsequent ADR treatment, or were treated with TNF-a (Sigma-Aldrich) at 50 mM for 30 min or 24 h. For GFP enrichment analyses of MSCV-SR-IRES-GFP-infected cells, changes in the percentage of GFP-positive cells prior to and after ADR exposure were normalized by the respective fractions of GFP-positive cells infected with an MSCV-GFP control vector. Cytospin preparations of suspension cultures for subsequent antigen-or SA-b-gal activity-detecting staining as well as in situ-SA-b-gal analyses in cryosections of snap-frozen lymph nodes were carried out as previously described (Schmitt et al 2002;Braig et al 2005;Reimann et al 2010).…”

Overexpression of von Hippel–Lindau protein synergizes with doxorubicin to suppress hepatocellular carcinoma in mice

“…Activated NF-jB translocates to the nucleus and binds to cognate sequences in the promoter region of over 60 genes involved in cell proliferation (cyclin D1), angiogenesis (VEGF), apoptosis (Bcl-2 family), and chemoresistance [12]. Inhibition of NF-jB activity enhances the efficacy of doxorubicin against various types of cancer [13,14]. NF-jB plays a key role in carcinogenesis and the progression of HCC [15].…”

Disruption of Protein–DNA Interactions: An Opportunity for Cancer Chemotherapy

“…Again owing to the complexity of the system, there are numerous up-stream cellular events that could lead to reduced NF-kB DNA binding activity as measured in cell extracts prepared from treated cells. A number of indirect NF-kB inhibitors has been identified such as pristimerin, an inhibitor of NF-kB-1 kinase (KINK-1) (Schon et al, 2008;Lu et al, 2010). While, the data demonstrate that cells treated with pristimerin had less NF-kB activation, this is an indirect effect, which, while being therapeutically useful, is not mediated by a direct interaction with NF-kB.…”