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Differential gene expression profiles induced by Hoechst dyes

ABSTRACT: Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear. The purpose of the present study is to determine the molecular mechanisms underlying different biological effects between H342 and H258. H2373 treated with H258 or H342

ORGANISM(S): Homo sapiens

SUBMITTER: naimei tang

PROVIDER: E-GEOD-28616 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.

Zhang Xinbo X Zhang Siyu Crystal SC Sun Dejun D Hu Jiang J Wali Anil A Pass Harvey H Fernandez-Madrid Felix F Harbut Michael R MR Tang Naimei N

PloS one 20111005 10

<h4>Background</h4>Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent ap ...[more]

PMID: 21998702

Similar Datasets

Differential gene expression profiles induced by Hoechst dyes

Project description:Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear. The purpose of the present study is to determine the molecular mechanisms underlying different biological effects between H342 and H258.

2011-04-16 | GSE28616 | GEO

Homo sapiens

Project description:Modulation of NF-kB-Dependent Gene Transcription Using Programmable DNA Minor Groove Binders

| PRJNA151489 | ENA

Molecular mechanism of DNA minor groove binding ligand as a radiation modulator

2011-08-01 | GSE30044 | GEO

Differential gene expression after gamma radiation in bis-benzimidazole-treated human glioblastoma using microarray analysis

2011-08-01 | GSE30043 | GEO

Differential gene expression after gamma radiation in bis-benzimidazole-treated human glioblastoma using microarray analysis

Project description:Radiation-induced DNA damage initiates a complex series of overlapping responses responsible for the maintenance of genome integrity. This study reports the expression analysis in response to DNA minor groove binding ligand (DMA-5-(4-methylpiperazin-1-yl)-2-[2’-(3,4-dimethoxyphenyl)-5`-benzimidazolyl] benzimidazole, an analogue of Hoechst 33342), with an emphasis on its ability to afford better protection in cells exposed to ionizing radiation. Four different types of samples were employed in the analysis: Control (untreated) cells, 50µM ligand-treated cells, 8.5Gy radiation-treated cells, and cells treated with 50µM ligand one hour prior to irradiation.

2011-07-31 | E-GEOD-30043 | biostudies-arrayexpress

Molecular mechanism of DNA minor groove binding ligand as a radiation modulator

Project description:Radiation-induced DNA damage initiates a complex series of overlapping responses responsible for the maintenance of genome integrity. This study reports the expression analysis in response to DNA minor groove binding ligand (DMA-5-(4-methylpiperazin-1-yl)-2-[2’-(3,4-dimethoxyphenyl)-5`-benzimidazolyl] benzimidazole, an analogue of Hoechst 33342), with an emphasis on its ability to afford better protection in cells exposed to ionizing radiation. Four different types of samples were employed in the analysis: Control (untreated) cells, 50µM ligand-treated cells, 2Gy radiation-treated cells, and cells treated with 50µM ligand one hour prior to 2Gy irradiation.

2011-07-31 | E-GEOD-30044 | biostudies-arrayexpress

Novel Minor Groove Binders cure animal African trypanosomiasis in an in vivo mouse model

Project description:Animal African trypanosomiasis (AAT) is a significant socioeconomic burden for sub-Saharan Africa because of its huge impact on livestock health. Existing therapies including those based on minor groove binders (MGBs), such as the diamidines, which have been used for decades, have now lost efficacy in some places because of the emergence of resistant parasites. Consequently, the need for new chemotherapies is urgent. Here, we describe a structurally distinct class of MGBs, Strathclyde MGBs (S-MGBs), which display excellent in vitro activities against the principal causative organisms of AAT: Trypanosoma congolense, and Trypanosoma vivax. We also show the cure of T. congolense-infected mice by a number of these compounds. In particular, we identify S-MGB-234, compound 7, as curative by using two applications of 50 mg/kg intraperitoneally. Crucially, we demonstrate that S-MGBs do not show cross-resistance with the current diamidine drugs and are not internalized via the transporters used by diamidines. This study demonstrates that S-MGBs have significant potential as novel therapeutic agents for AAT.

2022-01-18 | MTBLS882 | MetaboLights

Differential gene expression profiles of side population and non-side population cells of malignant pleural mesothelioma

Project description:Malignant pleural mesothelioma (MPM), which is associated with occupational asbestos exposure, is a deadly disease with no effective treatments due mainly to its high resistance to anti-cancer drugs. The molecular mechanisms responsible for its chemotherapeutic resistance are complicated and undefined. However, the presence of side population cells (SP cells) in tumors is a well-accepted explanation for their anti-cancer drug resistance. To identify SP cell-specific gene expression signature, microarray technique has been employed. Our data show differential gene expression profiles between SP and non-SP cells of H2714 mesothelioma cells. SP cells over-expressed genes associated with cancer stem cell (CSC) and drug resistance: DUSP6, SPRY2 and IL6, as well as multi-pathways, including the cancer stem cell-associated pathways Notch and c-Kit. Therefore, we believe that targeting CSC-specific genes and pathways in SP cells may hold the key to the discovery of effective treatments for reversing chemotherapeutic resistance to MPM treatment. 4 samples

2011-11-18 | E-GEOD-33734 | biostudies-arrayexpress

Estimating Genome-wide Off-Target Effects for Pyrrole-Imidazole Polyamide Binding by a Pathway-Based Expression Profiling Approach (CaSki cells)

Project description:Side and off-target effects remain a difficult issue in the search of pharmaceutical leads, especially with DNA-binding molecules or genome editing methods where the issue becomes particularly thorny. A particular case is the investigations into the off-target effects of N-methylpyrrole-N-methylimidazole polyamides, a naturally inspired class of DNA binders that discriminately access the minor groove with strong affinity and sequence specificity but the relatively short motif of < 20 bases often imply possible non-unique genomic binding. Multiple binding sites may translate to binding at non-intended loci, potentially leading to off-target effects, issues that very few approaches are able to address to-date. We here report an analytical method of inferring off-target binding from expression profiling based on the relative impact to various biochemical pathways, as well as an accompanying side effect prediction engine to allow candidate polyamides to be systematically screened. This method marks the first attempt in PI polyamide research to identify elements in various biochemical pathways sensitive to the treatment of a candidate polyamide to infer possible off-target effects. Expression changes were then considered for their possible effect on outward phenotypic changes, manifested as side effects, should the same PI polyamide candidate be administered clinically. We also performed a series of animal experiments to validate some of these effects, and found some corroboration in certain side effect manifestations, such as changes in the level of aspartate transaminase in ICR and nude mice after injection of some of the candidate polyamides in this study.

2019-04-09 | GSE124455 | GEO

Estimating Genome-wide Off-Target Effects for Pyrrole-Imidazole Polyamide Binding by a Pathway-Based Expression Profiling Approach (Kelly cells)

2019-04-09 | GSE124457 | GEO