Search results for " NF-κB"
showing 7 items of 17 documents
Antitumor effects of curcumin and structurally β-diketone modified analogs on multidrug resistant cancer cells
2007
Abstract Using concepts of bioisostery a series of curcumin analogs were synthesized: the diketonic system of the compound was elaborated into enaminones, oximes, and the isoxazole heterocycle. The cell growth inhibitory and apoptosis inducing effects of the new analogs were evaluated by in vitro assays in the hepatocellular carcinoma HA22T/VGH cells, as well as in the MCF-7 breast cancer cell line and in its multidrug resistant (MDR) variant MCF-7R. Increased antitumor activity on all cell lines was found with the isoxazole analog and especially with the benzyl oxime derivative; in the HA22T/VGH cell model, the latter compound inhibited constitutive NF-κB activation.
Mechanisms of Raf-1 Kinase Inhibitor Protein Dysregulation in Triple-Negative Breast Cancers and Identification of Possible Novel Therapeutic Approac…
2014
Triple-negative breast cancers (TNBCs) are a heterogenous group of breast cancers characterized by poor prognosis because they are not amenable to targeted therapies. We have taken into account that altered expression of Raf-1 kinase inhibitor protein (RKIP), a tumor and metastasis suppressor and a promoter of drug-induced apoptosis, is frequent in TNBCs and may be involved in their aggressive biology. Interestingly, the analysis of the possible mechanisms of RKIP downregulation in TNBCs permits the identification and recapitulation of different possible approaches, including epigenetic modulation, e.g., by DNA demethylating agents or histone deacetylase inhibition, and NF-κB inhibition. Th…
A Symphytum officinale Root Extract Exerts Anti-inflammatory Properties by Affecting Two Distinct Steps of NF-κB Signaling
2019
Symphytum officinale, commonly known as comfrey, constitutes a traditional medicinal plant with a long-standing therapeutic history, and preparations thereof have been widely used for the treatment of painful muscle and joint complaints, wound and bone healing, and inflammation. Today, its topical use is based on its analgesic and anti-inflammatory effects, which have been substantiated by modern clinical trials. However, the molecular basis of its action remained elusive. Here, we show that a hydroalcoholic extract of comfrey root impairs the development of a pro-inflammatory scenario in primary human endothelial cells in a dose-dependent manner. The extract, and especially its mucilage-de…
Pulsed Electric Fields Alter Expression of NF-κB Promoter-Controlled Gene
2021
The possibility to artificially adjust and fine‐tune gene expression is one of the key mile-stones in bioengineering, synthetic biology, and advanced medicine. Since the effects of proteins or other transgene products depend on the dosage, controlled gene expression is required for any ap-plications, where even slight fluctuations of the transgene product impact its function or other critical cell parameters. In this context, physical techniques demonstrate optimistic perspectives, and pulsed electric field technology is a potential candidate for a noninvasive, biophysical gene regulator, exploiting an easily adjustable pulse generating device. We exposed mammalian cells, transfected with a…
Toll signal transduction pathway in bivalves: Complete cds of intermediate elements and related gene transcription levels in hemocytes of immune stim…
2014
Based on protein domain structure and organization deduced from mRNA contigs, 15 transcripts of the Toll signaling pathway have been identified in the bivalve, Mytilus galloprovincialis. Identical searches performed on publicly available Mytilus edulis ESTs revealed 11 transcripts, whereas searches performed in genomic and new transcriptome sequences of the Pacific oyster, Crassostrea gigas, identified 21 Toll-related transcripts. The remarkable molecular diversity of TRAF and IKK coding sequences of C. gigas, suggests that the sequence data inferred from Mytilus cDNAs may not be exhaustive. Most of the Toll pathway genes were constitutively and ubiquitously expressed in M. galloprovinciali…
Synthesis of curcumin derivatives and analysis of their antitumor effects in triple negative breast cancer (TNBC) cell lines
2019
We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC50 in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least eq…
Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor {kappa}B.
2009
Cells of the monocyte-macrophage lineage play a central role in the orchestration and resolution of inflammation. Plasticity is a hallmark of mononuclear phagocytes, and in response to environmental signals these cells undergo different forms of polarized activation, the extremes of which are called classic or M1 and alternative or M2. NF-kappaB is a key regulator of inflammation and resolution, and its activation is subject to multiple levels of regulation, including inhibitory, which finely tune macrophage functions. Here we identify the p50 subunit of NF-kappaB as a key regulator of M2-driven inflammatory reactions in vitro and in vivo. p50 NF-kappaB inhibits NF-kappaB-driven, M1-polariz…