Search results for " c-Myc"
showing 10 items of 51 documents
Chemically modified tetracyclines induce cytotoxic effects against J774 tumour cell line by activating the apoptotic pathway
2003
Here, we have studied the effects of chemically modified tetracyclines (CMTs) on apoptosis both at the level of the cytoplasmic proteolytic caspase cascade, and on Bcl-2 and c-myc mRNA expression in the J774 macrophage cell line. The results indicate that CMTs induce morphological changes consistent with apoptotic events, as clearly demonstrated both by the acridine orange and ethidium bromide staining, and by TUNEL and fragmentation ELISA assays. Furthermore, the analysis of the cell cycle by flow cytometry shows an evident apoptotic sub-G0G1 peak, without important modifications in the cell cycle distribution. CMTs induce programmed cell death (PCD) in a dose-dependent manner and CMT-8 is…
MYC and EGR1 synergize to trigger tumor cell death by controlling NOXA and BIM transcription upon treatment with the proteasome inhibitor bortezomib
2014
The c-MYC (MYC afterward) oncogene is well known for driving numerous oncogenic programs. However, MYC can also induce apoptosis and this function of MYC warrants further clarification. We report here that a clinically relevant proteasome inhibitor significantly increases MYC protein levels and that endogenous MYC is necessary for the induction of apoptosis. This kind of MYC-induced cell death is mediated by enhanced expression of the pro-apoptotic BCL2 family members NOXA and BIM. Quantitative promoter-scanning chromatin immunoprecipitations (qChIP) further revealed binding of MYC to the promoters of NOXA and BIM upon proteasome inhibition, correlating with increased transcription. Both pr…
The apoptotic effects and synergistic interaction of sodium butyrate and MG132 in human retinoblastoma Y79 cells
1999
This study deals with the apoptotic effect exerted on human retinoblastoma Y79 cells by both sodium butyrate and an inhibitor of 26S proteasome [z-Leu-Leu-Leu-CHO (MG132)] and their synergistic effect. Exposure to sodium butyrate (1-4 mM) induced an accumulation of cells in the G2-M phase that was already visible after 24 h of treatment, when morphological and biochemical signs of apoptosis appeared only in a small number of cells (5-10%). Thereafter, the apoptotic effects increased progressively with slow kinetics, reaching a maximum after 72 h of exposure, when they concerned a large fraction of cells (>75% with 4 mM sodium butyrate). Sodium butyrate stimulated the conversion of procaspas…
Proteomic differentiation pattern in the U937 cell line
2011
The U937 cell line, originally established from a histiocytic lymphoma, has been widely used as a powerful in vitro model for haematological studies. These cells retain the immature cell phenotype and can be induced to differentiate by several factors, among which 12-O-tetradecanoyl-13-phorbol acetate (TPA). Fully differentiated cells acquire the adherent phenotype and exhibit various properties typical of macrophages. However, in spite of a great deal of research devoted to the U937 cellular model, the molecular basis of biological processes involved in the monocyte/macrophage differentiation remains unclear. The present study has been undertaken to contribute to this knowledge, in order t…
Multiple changes induced by fibroblasts on breast cancer cells.
2010
It is now widely recognised that the cross-talk between cancer and stromal cells may play a crucial role in cancer progression. However little is known about the complex underlying molecular mechanisms that occur within the tumor microenvironment. Fibroblasts are the major stromal cells with multiple roles, especially towards both the extracellular matrix and the neighbouring cell population, including neoplastic cells. Consequently, proteomic analyses would provide a wider resource for a better understanding of the potential modulating effects exerted by fibroblasts on cancer cells. In this report we describe the effects of fibroblast stimulation on the breast cancer cell line (8701-BC) pr…
GAM/ZFp/ZNF512B is central to a gene sensor circuitry involving cell-cycle regulators, TGF beta effectors, Drosha and microRNAs with opposite oncogen…
2010
MicroRNAs (miRNAs) are small regulatory RNAs targeting multiple effectors of cell homeostasis and development, whose malfunctions are associated with major pathologies such as cancer. Herein we show that GAM/ZFp/ZNF512B works within an intricate gene regulatory network involving cell-cycle regulators, TGFβ effectors and oncogenic miRNAs of the miR-17-92 cluster. Thus, GAM impairs the transcriptional activation of the miR-17-92 promoter by c-Myc, downregulates miR-17-92 miRNAs differentially, and limits the activation of genes responsive to TGFβ canonical pathway. In contrast, TGFβ decreases GAM transcripts levels while differentially upregulating miR-17-92 miRNAs. In turn, miR-17, miR-20a a…
Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives
2021
Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting ca…
NiII, and ZnII Schiff Base Complexes: Telomeric G-quadruplex Stabilizers
2014
Recently, NiII and ZnII metal complexes of the ligand Salpyrim have been synthesized and characterized. Their affinity for wild-type h-Telo G-quadruplex DNA and for calf thymus DNA was investigated by UV absorption spectroscopy, circular dichroism and viscometry. The data collectively suggest that both complexes bind effectively to G-quadruplexes by direct end-stacking, stabilizing the oligonucleotide secondary structure. The two complexes are also typical B-DNA intercalators. Remarkably, their binding constants, Kb, with the G4s structures are about 10 fold higher than those with B-DNA, highlighting the selectivity. Experiments to evaluate the biological activity of the two complexes again…
The Kelch protein NS1-BP interacts with alpha-enolase/MBP-1 and is involved in c-Myc gene transcriptional control
2007
Alpha-enolase is a key glycolytic enzyme that plays a functional role in several physiological processes depending on the cellular localization. The enzyme is mainly localized in the cytoplasm whereas an alternative translated form, named MBP-1, is predominantly nuclear. The MBP-1 protein has been characterized as a c-Myc promoter binding protein that negatively controls transcription. In the present study, we identified the kelch protein NS1-BP as one of the alpha-enolase/MBP-1 partners by using a yeast two-hybrid screening. Although NS1-BP has been originally described as a protein mainly localized in the nucleus, we provide evidence that NS1-BP also interacts with actin in human cells, a…
Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tub…
2020
Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3&prime