3 research outputs found
The DNA methylome of inflammatory bowel disease (IBD) reflects intrinsic and extrinsic factors in intestinal mucosal cells
Abnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be the consequence (and potential effector) of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a combined analysis of published DNA methylation data in intestinal mucosal cells of IBD and control samples. We identified abnormal DNA methylation at different levels: deviation from mean methylation signals at site and region levels, and differential variability. A fraction of such changes is associated with genetic polymorphisms linked to IBD susceptibility. In addition, by comparing with another intestinal inflammatory condition (i.e., coeliac disease) we propose that aberrant DNA methylation can also be the result of unspecific processes such as chronic inflammation. Our characterization suggests that IBD methylomes combine intrinsic and extrinsic responses in intestinal mucosal cells, and could point to knowledge-based biomarkers of IBD detection and progression.This work was supported by the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales [ANRS, Reference No. ECTZ47287 and ECTZ50137]; Institut National du Cancer (FR) [PLBIO 2017] (project: T cell tolerance to microbiota and colorectal cancers), and Ligue Contre le Cancer (FR) [AAP 2018]; NF is partially funded by the Basque Department of Health [project 2018/111086]
Different Cell Cycle Modulation in SKOV-3 Ovarian Cancer Cell Line by Anti-HIV Drugs
Anti-retroviral drugs used for the treatment of Human Immunodeficiency Virus (HIV) have proven to be effective even against cancer. Drawing from this background the aim of our research project was to evaluate the effects of anti-HIV drugs that belong to the Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI, abacavir and tenofovir), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI, efavirenz and etravirine) and Protease Inhibitors (PI, darunavir) on ovarian adenocarcinoma cell line (Skov-3). We observed by FACS analysis that the treatment with NRTI and NNRTI showed a block in G0/G1 phase. In particular etravirine (ETR) displayed a relevant block in the progression of the G0/G1 phase of the cell cycle compared with the other examined drugs and it was also able to induce differentiation of SKOV-3 cells. In contrast, FACS analysis demonstrated that, abacavir (ABC) and PI inhibitor darunavir (DRV) showed no effect on proliferation cancer cells. DAPI (4',6-diamidino-2-phenylindole) staining demonstrated that cells treated with the NNRTI (efavirenz and etravirine) presented more DNA damages compared with other treatments. Immunoblotting analysis demonstrated tenofovir (TDF), efavirenz (EFV) and etravirine to be able to obtain a reduction in the expression of cyclin D1, Rb hypophosphorylation and increase of p21 concentration. Finally we also observed that etravirine also induced differentiation as demonstrated by Western Blot with high levels of E-cadherin expression. Therefore our study provides additional evidence supporting the in vitro cytotoxic effects of etravirine and efavirenz; furthermore it promotes the hypothesis for their potential use as therapeutic agents in ovarian cancer