Similar Datasets
Project description:Antitumour activity of Micromeria fruticosa on Cancer Cell Lines
| PRJNA478954 | ENA
Project description:Targeting quadruplexes in cancer genes and pathways by a novel class of asymmetrically-substituted napththalene diimides (SOP1812) with potent cellular and antitumour activity in models for pancreatic cancer.
2020-06-04 | GSE151741 | GEO
Project description:Introduction: The flavonoid myricetin has been shown to induce cell cycle arrest and mitochondrial-dependent apoptosis in preclinical cancer models. We hypothesised that myricetin-derived flavonoids with redox properties and improved physicochemical attributes that enhance cell uptake and mitochondrial targeting might have increased potential as antitumour agents, since mitochondria are the main site of production of reactive oxygen species (ROS) and redox status is known to regulate the development and advancement of certain cancers. In this study we assessed a small library of novel flavonoids, then focussed on the lead compound, second-generation analogue OncamexTM, its mechanism of action and structure-activity relationships as an anti-proliferative agent. Methods: With this aim, we studied the effect of OncamexTM in a panel of 7 breast cancer cell lines using proliferation, cytotoxicity and apoptosis assays. The redox properties and mitochondrial delivery of the drug were studied using cyclic voltammetry and fluorescence microscopy, respectively. The mechanism of action was further studied using western blotting, gene expression analysis and immunohistochemistry (IHC) of treated xenograft tissue from in vivo mice models. Results: Sulforhodamine B (SRB) proliferation assays demonstrated strong, anti-proliferative properties of OncamexTM, with IC50 values in the low micromolar range. Treatment for 8 h exerted concentration-dependent reduction in cell viability and induction of cytotoxicity and apoptosis, with increased caspase activation. Microarray analysis suggested that OncamexTM regulates changes in cell cycle and apoptosis at gene expression level. Fluorescence microscopy was used to investigate mitochondrial targeting and ROS regulation in treated cells. OncamexTM was found to induce production of superoxide at concentrations which exerted anti-proliferative effects. Initial in vivo studies in mice implanted with a MDA-MB-231 breast cancer xenograft showed that OncamexTM inhibited tumour growth, reducing tissue viability and Ki-67 proliferation, with no overall systemic toxicity. Conclusions: OncamexTM is a novel flavonoid capable of specific delivery to the mitochondria and induction of ROS production. We have shown its antitumor activity in preclinical models of breast cancer, both in vitro and in initial in vivo models, where tumour growth was arrested without inducing toxicity, support the potential of this novel drug for its continued development as an anticancer agent. Total RNA was obtained from 5 breast cancer cell lines subjected to 6 hours of 10µM OncamexTM and matched untreated controls (1% DMSO)
2015-09-01 | E-GEOD-70949 | biostudies-arrayexpress
Project description:To investigate mechanisms of resistance to BRAF inhibitor therapy in melanoma, BRAF mutant cell lines have been chronically exposed to BRAFi to create phenotypes with acquired drug resistance. Activity-based protein profiling with desthiobiotinylating ATP probes (ActivX, Thermo) is used to examine the differences between naive and drug-resistant cells.
2016-12-13 | PXD004343 | Pride
Project description:The antitumour activity of a hit tioxanthone is associated with alterations in cholesterol localization We used microarrays to detail the global programme of gene expression underlying treatment of lung cancer with TXA1.Hcl
2018-12-24 | GSE110825 | GEO
Project description:The purpose of this study is to investigate certain genes inuduced/reduced by NK150460, novel compound possessing antitumor activity. To identify genes, time course samples were prepared from NK150460 sensitive and insensitive breast cancer cell lines. By comparing patterns in both sensitive and resistant cell lines, we tried to identify genes specifically modulated by NK150460 treatment.
2014-09-19 | GSE61548 | GEO
Project description:Ortega2013 - Interplay between secretases
determines biphasic amyloid-beta level
This model is described in the article:
Interplay between ?-, ?-,
and ?-secretases determines biphasic amyloid-? protein level in
the presence of a ?-secretase inhibitor.
Ortega F, Stott J, Visser SA,
Bendtsen C.
J. Biol. Chem. 2013 Jan; 288(2):
785-792
Abstract:
Amyloid-? (A?) is produced by the consecutive cleavage of
amyloid precursor protein (APP) first by ?-secretase,
generating C99, and then by ?-secretase. APP is also cleaved by
?-secretase. It is hypothesized that reducing the production of
A? in the brain may slow the progression of Alzheimer disease.
Therefore, different ?-secretase inhibitors have been developed
to reduce A? production. Paradoxically, it has been shown that
low to moderate inhibitor concentrations cause a rise in A?
production in different cell lines, in different animal models,
and also in humans. A mechanistic understanding of the A? rise
remains elusive. Here, a minimal mathematical model has been
developed that quantitatively describes the A? dynamics in cell
lines that exhibit the rise as well as in cell lines that do
not. The model includes steps of APP processing through both
the so-called amyloidogenic pathway and the so-called
non-amyloidogenic pathway. It is shown that the cross-talk
between these two pathways accounts for the increase in A?
production in response to inhibitor, i.e. an increase in C99
will inhibit the non-amyloidogenic pathway, redirecting APP to
be cleaved by ?-secretase, leading to an additional increase in
C99 that overcomes the loss in ?-secretase activity. With a
minor extension, the model also describes plasma A? profiles
observed in humans upon dosing with a ?-secretase inhibitor. In
conclusion, this mechanistic model rationalizes a series of
experimental results that spans from in vitro to in vivo and to
humans. This has important implications for the development of
drugs targeting A? production in Alzheimer disease.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000556.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2014-10-23 | BIOMD0000000556 | BioModels
Project description:To investigate the effects of loss of LSD1 (KDM1A) on differential gene expression, we treated two cell lines of small cell lung cancer with 1 M LSD1 inhibitor ORY-1001 or vehicle control for 10 days. We then performed gene expression profiling analysis on treated and control cells for each of the two cell lines.
2022-06-13 | GSE205880 | GEO
Project description:Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file).
2012-10-12 | GSE41499 | GEO
Project description:Cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex CRL4CRBN, is the target of the immunomodulatory drugs lenalidomide and pomalidomide. Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of two common substrates, transcription factors Aiolos and Ikaros. Here we report that the pleiotropic pathway modifier CC-122, a new chemical entity termed pleiotropic pathway modifier binds CRBN and promotes degradation of Aiolos and Ikaros in diffuse large B-cell lymphoma (DLBCL) and T cells in vitro, in vivo and in patients, resulting in both cell autonomous as well as immunostimulatory effects. In DLBCL cell lines, CC-122-induced degradation or shRNA mediated knockdown of Aiolos and Ikaros correlates with increased transcription of interferon stimulated genes (ISGs) independent of interferon α, β, γ production and/or secretion and results in apoptosis in both ABC and GCB-DLBCL cell lines. Our results provide mechanistic insight into the cell of origin independent anti-lymphoma activity of CC-122, in contrast to the ABC subtype selective activity of lenalidomide. Microarray analysis of the OCI-LY10 activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell line treated with the compound CC-122 for 18 hours
2015-11-26 | E-GEOD-75420 | biostudies-arrayexpress