Search results for "DNA METHYLATION"
showing 10 items of 392 documents
UPREGULATION OF MIR-29A AND GENOMIC DNA HYPERMETHYLATION IN NORMAL KARYOTYPE AML SHOWING DNMT3A MUTATION UPREGOLAZIONE DEL MIR-29A E IPERMETILAZIONE …
2015
DNMT3A, a member of DNA methyltransferases, is mutated in approximately 22% of de novo normal karyotype acute myeloid leukemia (NK-AML) patients leading to adverse overall survival. The highly recurrent mutation in DNMT3A is a “gain of function-like” at codon R882. To indagate about miRNA signature in NK-AML R882-DNMT3A mutated we studied by qRT-PCR the expression of 384 known human miRNA in 9 selected de-novo AML DNMT3A mutated. We compared miRNA expression data with our previous results obtained in 31 AML DNMT3A wild type (WT) and we focused on a strong up-regulation of miR155, miR29a, miR196b and miR25. We consolidated this data in additional 24 new DNMT3A mutated AML and we confirmed th…
Fifteen years’ experience treating cells with inorganic arsenic, a molecule able to induce genetic / genomic instability and epigenetic changes even …
2016
Treating V79-Cl3 cells with 10 µM sodium arsenite (SA) for 24h we observed severe alterations in spindle morphology and aneuploidy; treating rat astrocytes with SA we detected HSP70 induction and DNA damage. We assumed that SA induced in dividing cells early genetic instability. Subsequently, we in vitro stabilized those V79-Cl3 cells dividing at the end of SA-treatment and maintained for long without SA (ASO cells). In ASO cells, we observed chromosomal rearrangements, increased spontaneous mutations, genome-wide DNA hypomethylation (GWDH), similarly to exposed cells. We inferred that a short-term SA exposure has long-term effects and that GWDH enhances the genetic instability. Consequentl…
Methylation decrease of BECN1 gene induced by phytochemical Indicaxantin in Caco2 cells: an epigenetic hypothesis of autophagy
2014
Autophagy is a highly conserved catabolic process that degrades and recycles intracellular components through the lysosomes [1]. The role of this process in tumorigenesis and tumor progression is controversial: in the early stages, it can block tumor growth and conversely it can promote its progression in the later stages [2]. The tumor suppressor BECN1 gene, encodes the protein Beclin 1, a marker of autophagy down-regulated in several types of cancer, such as colorectal cancer [3]. There are a lot of both genetic and environmental risk factors for colorectal cancer, including diet: for this reason, in accordance with epidemiological studies, consumption of foods rich in phytochemicals is w…
Can Early Life Exposure to Permethrin lead to intergenerational effects?
2016
Pesticides are largely used in agriculture against pests and consequently are present in fruits and vegetables. The wide presence of pesticide residues in breast milk underline the risk for the population, focalizing the long-term consequence of early life pyrethroid exposure. The significant presence of pyrethroid metabolites in the urine of population over the world confirms that their presence in food is a global problem. It has been demonstrated that there is a correlation between the environmental exposure to pesticides and the development of neurodegenerative diseases. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce neurodegeneration…
Persistent dysregulation of DNA methylation in cells with arsenic-induced genomic instability
2009
The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. In previous studies long-term progression of chromosomal instability was typified by increasing aneuploidy in Chinese hamster V79 and human keratinocyte cells treated with arsenite for a 24 hr exposure period followed by growth in arsenic-free medium for 40-120 cell generations. In the current study the role of progressive DNA methylation changes was evaluated in long-term cell cultures after brief arsenite treatments as above. We have found altered genomic methylation patterns in cells that were briefly exposed to arsenic with evidence for widespread dysregulation of CpG methylati…
Antiproliferative and pro-apoptotic effects of the phytochemical Indicaxanthin on human intestinal (Caco-2) and hepatic (Ha 22T) cancer cell lines
2012
In the present study antiproliferative effects of Indicaxanthin (Ind), a highly bioavailable pigment from the fruits of Opuntia ficus-indica (1), were investigated on a number of human cancer cell lines including hepatocarcinoma cells (HepG2, Ha22T, HUH 7), breast cancer cells (MCF7), cervix epithelial carcinoma (HeLa), and colorectal carcinoma cells (Caco-2). Cytotoxicity of Ind, in a concentration range between 25 to 100 M, was evaluated by Trypan blue exclusion method and MTT assay. Ind caused a clear dose- and time-dependent decrease in the proliferation of Caco-2 and Ha 22T cells with an IC(50) of about 50 M, with minor effect on the other cell lines. Flow cytometric analysis after A…
IL-1β maintains the DNA hypermethylation of anti-inflammatory IL-10 gene in a human intestinal epithelial cell line
2014
Intestinal inflammation is a natural process crucial to maintain gut integrity, but its deregulation is involved in the pathogenesis of severe intestinal disorders[1]. Intestinal epithelial cells play a crucial role in the inflammatory response, modulating the immune cell exposure to antigens and by their ability to secrete many inflammatory mediators. IL-1β represents a pivotal player: secreted by infiltrated leucocytes, it induces the expression of several pro-inflammatory genes. Also the anti-inflammatory IL-10, whose function is to terminate the inflammatory process, modulates the intestinal physiology[2]. Recent clinical reports showed that patients with ulcerative colitis in remission…
Jay Amin Hydroxamic Acid (JAHA), a histone deacetylase inhibitor with cytotoxic activity and the property to increase DNA repair of triple-negative M…
2017
Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination o…
Upregulation of miR-29a and genomic DNA hypermethylation in normal karyotype AML showing DNMT3A mutation
2015
Acute Myeloid Leukaemia (AML) is frequently associated to normal karyotype and DNMT3A mutations (R882). Since we previously demonstrated distinctive miRNA expression in some AML groups, we study 384 miRNA in 9 selected DNMT3A-mutated NK-AML patients. Comparing these data with our previous results obtained in 31 DNMT3A-unmutated AML, we focused on a significant up-regulation of miR-155, miR-29a, miR-196b and miR-25. We investigated expression of these miRNAs in additional 24 DNMT3A-mutated AML patients and we confirm the up-regulation of miR-155, miR-29a and miR-196b; in particular, we judged very interesting the over expression of miR-29a since is known to directly target DNMT3A, TET1 and T…
Value of polymorphisms and DNA methylation for the expression of CYP2E1 enzyme: implications in pharmacogenomics
2014
Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and DNA methylation of the 5′ flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associated with the incr…