- Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC) -
Hôpital Kirchberg -
9, rue Edward Steichen -
L-2540 Luxembourg
Luxembourg - +352-24684055
Research Interests: Cell Cycle, Drug metabolism, Apoptosis, Signal Transduction, Humans, and 11 moreAnimals, Detoxification, Signal Transduction Pathway Models, Polycyclic Aromatic Hydrocarbon, Mitogen Activated Protein Kinase, Enzyme, Aryl Hydrocarbon Receptor, Protein Expression, Cell Cycle regulation, BIOCHEMICAL PHARMACOLOGY, and Environmental Pollutants
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Valproic acid (VPA) exhibits important pharmacological properties but has been reported to trigger side effects, notably on the hematological system. We previously reported that VPA affects hematopoietic homeostasis by inhibiting... more
Valproic acid (VPA) exhibits important pharmacological properties but has been reported to trigger side effects, notably on the hematological system. We previously reported that VPA affects hematopoietic homeostasis by inhibiting erythroid differentiation and promoting myeloid and megakaryocyte differentiation. Here, we analyzed the effect of VPA on regulatory factors involved in erythro-megakaryocytic differentiation pathways, including transcription factors and microRNAs (miRs). We demonstrate that VPA inhibited erythroid differentiation in erythropoietin (Epo)-stimulated TF1 leukemia cells and CD34(+)/hematopoietic stem cells (HSCs) and in aclacinomycin-(Acla)-treated K562 cells. Mir-144/451 gene expression was decreased in all erythroid and megakaryocyte models in correlation with GATA-1 inhibition. In Epo-stimulated CD34(+)/HSCs, VPA induced the expression of the ETS family transcription factors PU.1, ETS-1, GABP-α, Fli-1 and GATA-2, which are all known to be negative regulator...
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Despite recent advances in the treatment of chronic myelogenous leukemia (CML), the development of drug resistance and minimal residual disease remain major challenges for the treatment of CML patients, thus highlighting the need to... more
Despite recent advances in the treatment of chronic myelogenous leukemia (CML), the development of drug resistance and minimal residual disease remain major challenges for the treatment of CML patients, thus highlighting the need to develop innovative new approaches to improve therapeutic outcome. Myrtucommulone A (MCA) is a nonprenylated acylphloroglucinol isolated from the leaves of myrtle, a plant traditionally used in folk medicine. To date, studies addressing bioactivities of myrtle and its specific components are rare. Here, we investigated the biological effects of MCA, focusing on its anti-leukemic activity. As evidenced by fragmented nuclei after Hoechst/propidium iodide staining and poly (ADP-ribose) polymerase cleavage, MCA induces apoptosis in CML cells through down-regulation of anti-apoptotic proteins. Interestingly, we showed that chronic treatment with MCA at low doses induced senescence in CML cells. Taken together, this study highlights the chemotherapeutical poten...
Over-expression of glutathione S-transferase P1 is related to chemotherapeutic drug resistance as well as to differentiation of human erythroleukemia cells. In opposition to previously described differentiating inducers which enhance the... more
Over-expression of glutathione S-transferase P1 is related to chemotherapeutic drug resistance as well as to differentiation of human erythroleukemia cells. In opposition to previously described differentiating inducers which enhance the GST-resistance phenotype, time- and concentration-dependent activation of both erythroid and megakaryocytic differentiation pathways by butyric acid progressively diminished GSTP1 mRNA expression. GSTP1 mRNA expression decreased by 25% (p<0.01) and 64% (p<0.01) in 1mM and 2mM butyric acid-differentiated K562 cells, respectively. These results were associated to both a reduction of GATA-1 binding activity to the GSTP1 promoter and to a posttranscriptional destabilization of GSTP1 mRNA in a concentration dependent manner. Indeed, GSTP1 mRNA half-life decreased from 43.8 to 36.2 h and 12.6 h in 1mM- and 2mM-treated cells, respectively.
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Research Interests: Kinetics, Environmental Health, Transcription Regulation, Gene expression, Biological Sciences, and 21 moreMolecular and cellular biology, Humans, Mice, Fossil Fuels, Animals, Histone Modification, HIstone Deacetylase, Heavy Metal, Chromatin remodeling, Chromium, Detoxification, Polycyclic Aromatic Hydrocarbon, Carcinogens, Enzyme, Aryl Hydrocarbon Receptor, Chromatin structure, Histones, DNA binding, Histone Acetylation, Histone deacetylase inhibitors, and Histone deacetylases
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In recent years, colorectal cancer (CRC) incidence has been increasing to become a major cause of morbidity and mortality worldwide from cancers, with high rates in westernized societies and increasing rates in developing countries.... more
In recent years, colorectal cancer (CRC) incidence has been increasing to become a major cause of morbidity and mortality worldwide from cancers, with high rates in westernized societies and increasing rates in developing countries. Epigenetic modifications including changes in DNA methylation, histone modifications, and non-coding RNAs play a critical role in carcinogenesis. Epidemiological data suggest that, in comparison to other cancers, these alterations are particularly common within the gastrointestinal tract. To explain these observations, environmental factors and especially diet were suggested to both prevent and induce CRC. Epigenetic alterations are, in contrast to genetic modifications, potentially reversible, making the use of dietary agents a promising approach in CRC for the development of chemopreventive strategies targeting epigenetic mechanisms. This review focuses on CRC-related epigenetic alterations as a rationale for various levels of prevention strategies and their potential modulation by natural dietary compounds.
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Research Interests: Organic Chemistry, Medicinal Chemistry, Enzyme Inhibitors, Chemical, Humans, and 22 moreVirtual screening, HIstone Deacetylase, Drug Design, Quantitative Structure Activity Relationship, Enzyme Inhibition, Histones, Coumarins, Medicinal, Acetylation, THEORETICAL AND COMPUTATIONAL CHEMISTRY, Experimental Validation, Cell Proliferation, Thiazoles, Structure activity Relationship, Cell Cycle Proteins, Cell Survival, Hydroxamic Acids, Antineoplastic Agents, Molecular Structure, Histone deacetylase inhibitors, Histone deacetylases, and Cell Growth
Chemoprevention is a promising anti-cancer approach with reduced secondary effects in comparison to classical chemotherapy. Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L.... more
Chemoprevention is a promising anti-cancer approach with reduced secondary effects in comparison to classical chemotherapy. Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. that allows suppression, retardation or inversion of carcinogenesis. Curcumin is also described as an anti-tumoral, anti- oxidant and anti-inflammatory agent capable of inducing apoptosis in numerous cellular systems.
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Research Interests: Genetics, Toxicology, Cancer, Cell Cycle, DNA replication, and 24 moreGene Silencing, Mice, Animals, Hepatocellular Carcinoma, DNA methylation, CpG islands, Carcinogens, Repression, Aryl Hydrocarbon Receptor, Cdk, Retinoblastoma, Tumor Suppressor Gene, Den, Transforming Growth Factor Beta, Disease Progression, Cell Proliferation, Base Sequence, AHR, ARNT, Diethylnitrosamine, All, retinoblastoma protein (RB1)., Liver Tumor, and Transforming Growth Factor
Research Interests: Nonparametric Statistics, Neurochemistry, Drosophila melanogaster, Cell line, Humans, and 10 moreAnimals, Chromatin Immunoprecipitation, Histone deacetylase inhibitor, Transfection, Protein Binding, Hydroxamic Acids, Neurosciences, Gene Expression Regulation, Histone deacetylase inhibitors, and Histone deacetylases
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Leukemogenesis is a multistep process in which successive transformational events enhance the ability of a clonal population arising from hematopoietic progenitor cells to proliferate, differentiate and survive. Clinically and... more
Leukemogenesis is a multistep process in which successive transformational events enhance the ability of a clonal population arising from hematopoietic progenitor cells to proliferate, differentiate and survive. Clinically and pathologically, leukemia is subdivided into four main categories: chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphocytic leukemia and acute myeloid leukemia. Leukemia has been previously considered only as a genetic disease. However, in recent years, significant advances have been made in the elucidation of the leukemogenesis-associated processes. Thus, we have come to understand that epigenetic alterations including DNA methylation, histone modifications and miRNA are involved in the permanent changes of gene expression controlling the leukemia phenotype. In this article, we will focus on the epigenetic defects associated with leukemia and their implications as biomarkers for diagnostic, prognostic and therapeutic applications.