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Gaascht F.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Dicato M.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Diederich M.,Seoul National University
Genes and Nutrition | Year: 2015

Coffee is the second most popular beverage in the world after water with a consumption of approximately two billion cups per day. Due to its low cost and ease of preparation, it is consumed in almost all countries and by all social classes of the population through different modes of preparation. Despites its simple appearance, a cup of coffee is in fact a complex mixture that contains hundreds of molecules, the composition and concentration of which vary widely and depend on factors including the origin of the coffee tree or its metabolism. Although an excessive consumption of coffee can be harmful, many molecules that are present in this black decoction exert anticancer properties. This review aims to describe the different primary coffee-containing substances that exert chemopreventive and bioactive activities against the different hallmarks and enabling characteristics of cancer, thus explaining the anticancer health benefit of black coffee. © 2015, Springer-Verlag Berlin Heidelberg.


PubMed | National Research Center of Egypt, University of Zagreb, Seoul National University, National and Kapodistrian University of Athens and Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc
Type: | Journal: Steroids | Year: 2016

Seven new (1-3, 5 and 8-10) and three previously reported (4, 6 and 7) 4-methylated steroids were isolated from the organic extract of the gorgonian Litophyton mollis. The structures and the relative configurations of the isolated natural products were determined on the basis of extensive analyses of their NMR and MS data. Metabolites 1 and 5-8 exhibited cytotoxic activity against K562 human chronic myelogenous leukemia cells with IC


De Bosscher K.,Ghent University | Beck I.M.,Ghent University | Dejager L.,VIB | Dejager L.,Ghent University | And 13 more authors.
Cellular and Molecular Life Sciences | Year: 2014

Glucocorticoids (GCs) block inflammation via interference of the liganded glucocorticoid receptor (GR) with the activity of pro-inflammatory transcription factors NF-κB and AP-1, a mechanism known as transrepression. This mechanism is believed to involve the activity of GR monomers. Here, we explored how the GR monomer-favoring Compound A (CpdA) affects AP-1 activation and activity. Our results demonstrate that non-steroidal CpdA, unlike classic steroidal GCs, blocks NF-κB- but not AP-1-driven gene expression. CpdA rather sustains AP-1-driven gene expression, a result which could mechanistically be explained by the failure of CpdA to block upstream JNK kinase activation and concomitantly also phosphorylation of c-Jun. In concordance and in contrast to DEX, CpdA maintained the expression of the activated AP-1 target gene c-jun, as well as the production of the c-Jun protein. As for the underlying mechanism, GR is a necessary intermediate in the CpdA-mediated gene expression of AP-1-regulated genes, but seems to be superfluous to CpdA-mediated JNK phosphorylation prolongation. The latter phenomenon concurs with the inability of CpdA to stimulate DUSP1 gene expression. ChIP analysis demonstrates that DEX-activated GR, but not CpdA-activated GR, is recruited to AP-1-driven promoters. Furthermore, in mice we observed that CpdA instigates a strong enhancement of TNF-induced AP-1-driven gene expression. Finally, we demonstrate that this phenomenon coincides with an increased sensitivity towards TNF lethality, and implicate again a role for JNK2. In conclusion, our data support the hypothesis that a ligand-induced differential conformation of GR yields a different transcription factor cross-talk profile. © 2013 The Author(s).


Radogna F.,University of Rome Tor Vergata | Radogna F.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Albertini M.C.,Urbino University | De Nicola M.,University of Rome Tor Vergata | And 3 more authors.
Mitochondrion | Year: 2015

Extra-neurological functions of melatonin include control of the immune system and modulation of apoptosis. We previously showed that melatonin inhibits the intrinsic apoptotic pathway in leukocytes via stimulation of high affinity MT1/MT2 receptors, thereby promoting re-localization of the anti-apoptotic Bcl-2 protein to mitochondria. Here we show that Bcl-2 sequesters pro-apoptotic Bax into mitochondria in an inactive form after melatonin treatment, thus reducing cell propensity to apoptosis. Bax translocation and the anti-apoptotic effect of melatonin are strictly dependent on the presence of Bcl-2, and on the 5-lipoxygenase (5-LOX) metabolite 5-hydroxyeicosatetraenoic acid (5-HETE), which we have previously shown to be produced as a consequence of melatonin binding to its low affinity target calmodulin. Therefore, the anti-apoptotic effect of melatonin requires the simultaneous, independent interaction with high (MT1/MT2) and low (calmodulin) affinity targets, eliciting two independent signal transduction pathways converging into Bax sequestration and inactivation. MT1/MT2 vs. lipoxygenase pathways are activated by 10-9 vs. 10-5M melatonin, respectively; the anti-apoptotic effect of melatonin is achieved at 10-5M, but drops to 10-9M upon addition of exogenous 5-HETE, revealing that lipoxygenase activation is the rate-limiting pathway. Therefore, in areas of inflammation with increased 5-HETE levels, physiological nanomolar concentrations of melatonin may suffice to maintain leukocyte viability. © 2015 © Elsevier B.V. and Mitochondria Research Society.


PubMed | Seoul National University and Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc
Type: Journal Article | Journal: Genes & nutrition | Year: 2015

Coffee is the second most popular beverage in the world after water with a consumption of approximately two billion cups per day. Due to its low cost and ease of preparation, it is consumed in almost all countries and by all social classes of the population through different modes of preparation. Despites its simple appearance, a cup of coffee is in fact a complex mixture that contains hundreds of molecules, the composition and concentration of which vary widely and depend on factors including the origin of the coffee tree or its metabolism. Although an excessive consumption of coffee can be harmful, many molecules that are present in this black decoction exert anticancer properties. This review aims to describe the different primary coffee-containing substances that exert chemopreventive and bioactive activities against the different hallmarks and enabling characteristics of cancer, thus explaining the anticancer health benefit of black coffee.


PubMed | Seoul National University and Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc
Type: Review | Journal: Molecules (Basel, Switzerland) | Year: 2016

The remarkable complexity of cancer involving multiple mechanisms of action and specific organs led researchers Hanahan and Weinberg to distinguish biological capabilities acquired by cancer cells during the multistep development of human tumors to simplify its understanding. These characteristic hallmarks include the abilities to sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, avoid immune destruction, and deregulate cellular energetics. Furthermore, two important characteristics of tumor cells that facilitate the acquisition of emerging hallmarks are tumor-promoting inflammation and genome instability. To treat a multifactorial disease such as cancer, a combination treatment strategy seems to be the best approach. Here we focus on natural histone deacetylase inhibitors (HDACi), their clinical uses as well as synergies with modulators of the pro-inflammatory transcription factor signaling pathways.


Sibille E.,University of Lorraine | Bana E.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Bana E.,University of Lorraine | Chaouni W.,University of Lorraine | And 3 more authors.
Analytical Biochemistry | Year: 2012

The cell division cycle 25 phosphatases (CDC25s) are key regulators of the physiological cell cycle progression. Their overexpression has been reported in a significant number of cancers, and their inhibition appears to be an interesting strategy for treatments. We propose here a rapid screening test allowing the detection of reversible and irreversible CDC25A and -C inhibitors. The test is based on the incubation of the candidate molecules with the human CDC25 proteins followed by an ultrafiltration step. The retentate is then directly analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOFMS) to detect reversible inhibitors or submitted to peptide mass fingerprint (PMF) analysis to reveal irreversible inhibitors covalently bound to the protein active site. After its validation, the protocol is applied to the detection of a novel candidate inhibitor of CDC25s named SV37. The screening procedure, as well as the preliminary biological results, demonstrates that this compound behaves as a reversible inhibitor. © 2012 Elsevier Inc. All rights reserved.


Chateauvieux S.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Grigorakaki C.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Morceau F.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Dicato M.,Center Hospitalier Of Luxembourg | Diederich M.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc
Biochemical Pharmacology | Year: 2011

Erythropoietin (EPO) is a glycoprotein that is mainly produced in the adult kidney, and it was initially highlighted for its action on the hematopoietic system. Moreover, EPO is also expressed in several non-hematopoietic tissues, where it plays a role in the protection from apoptosis and inflammation due to hypoxia, toxicity or injury. These protective effects are mainly known and studied in cardioprotection and neuroprotection but are also reported in retina degeneration, auditory injury and pancreatic-related diseases. The tissue protective effect of EPO is mainly mediated through the interaction with the heterodimeric receptor EPOR/βcR. Human recombinant EPO (HuREPO), which has been developed to treat anemia, is not adequate for tissue protection. The low affinity of the alternative receptor for EPO involves the injection of excessive concentration of erythropoiesis-stimulating agents (ESAs), implicating side effects due to the cross-talk with hematopoietic activity. For these reasons, EPO derivatives with less affinity for the EPO homodimeric receptor are under development. In this review, we provide an overview of the erythroid and non-erythroid functions of EPO by detailing the molecular mechanisms activated by the binding of EPO to its receptors in different tissues. © 2011 Elsevier Inc. All rights reserved.


Diederich M.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Chateauvieux S.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Morceau F.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Dicato M.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc
Journal of Biomedicine and Biotechnology | Year: 2010

Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties. © 2010 Sbastien Chateauvieux et al.


Chateauvieux S.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Eifes S.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Morceau F.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | Grigorakaki C.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer Lbmcc | And 4 more authors.
Biochemical Pharmacology | Year: 2011

As a histone deacetylase inhibitor, valproic acid (VPA) is a candidate for anticancer therapy. Besides, VPA exhibits various mechanisms of action and its effects on the molecular basis of hematopoiesis remain unclear. To study the effects of VPA on the hematopoietic system, we performed microarray analysis using K562 cells treated with 1 mM VPA over a 72 h time course. The association between gene ontology (GO) terms and the lists of differentially expressed genes was tested using the Bioconductor package GOstats. Enrichment analysis for cellular differentiation pathways was performed based on manually curated gene lists. Results from microarray analysis were confirmed by studying cell differentiation features at the molecular and cellular levels using other hematopoietic cell lines as well as hematopoietic stem/progenitor CD34 + cells. Microarray analysis revealed 3440 modulated genes in the presence of VPA. Genes involved in the granulo-monocytic differentiation pathway were up-regulated while genes of the erythroid pathway were down-regulated. This was confirmed by analyzing erythrocytic and myeloid membrane markers and lineage-related gene expression in HEL, MEG01, HL60 as well as CD34+ cells. Moreover, GATA-1 and its co-factors (FOG1, SP1) were down-regulated, while myelopoiesis activator PU.1 was up-regulated, in agreement with an inhibition of erythropoiesis. Our functional profiling and cell phenotyping approach demonstrates that VPA is able to alter hematopoietic homeostasis by modifying the cell population balance in the myeloid compartment. This may lead to a potential failure of erythropoiesis in patients with cancer or chronic inflammatory diseases having a well-described propensity to anemia. © 2010 Elsevier Inc.

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