Anticancer properties of distinct antimalaria drug classes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51739 | GEO | 2013/10/26
SECONDARY ACCESSION(S): PRJNA224735
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Antimalarials have anticancer potential. Results: We have systematically tested five distinct antimalaria drugs in a panel of cancer cell lines. Conclusion: Three antimalarial classes display potent antiproliferative activity, and their potency is correlated with cancer cell gene expression patterns. Significance: We confirm and extend anticancer potential of these antimalarials and we discuss their therapeutic potential based on clinical data. Key words: Malaria, Anticancer drug, Drug Discovery, Genomics, Gene Expression, Bioinformatics, Cancer AffymetrixM-BM-. HG-U133 Plus 2.0 mRNA expression arrays were used to determine the expression. CEL result files were pre-processed using the RMA (Irizarry et al, 2003) algorithm. This microarray analysis was performed for 91 cell lines.
2013-10-26 | E-GEOD-51739 | biostudies-arrayexpress
Project description:The increasing spread of drug-resistant malaria strains underscores the need for new antimalarial agents with novel modes of action (MOAs). Here, we describe a compound representative of a new class of antimalarials. This molecule, ACT-213615, potently inhibits in vitro erythrocytic growth of all tested Plasmodium falciparum strains, irrespective of their drug resistance properties, with IC(50) values in the low single-digit nanomolar range. Like the clinically used artemisinins, the compound equally and very rapidly affects all three asexual erythrocytic parasite stages. In contrast, microarray studies suggest that the MOA of ACT-213615 is different from that of the artemisinins and other known antimalarials. ACT-213615 is orally bioavailable in mice, exhibits activity in the murine P. berghei model and efficacy comparable to that of the reference drug chloroquine in the recently established P. falciparum SCID mouse model.ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potential. Histone deacetylase (HDACs) inhibitors are being intensively pursued as potential new antimalarial drugs, and are also emerging as valuable tools for investigating transcriptional control in malaria parasites. In this study, the genome-wide transcriptional effects of three structurally related hydroxamate HDAC inhibitors were profiled in Plasmodium falciparum, the most lethal of the malaria parasite species that infects humans. Trophozoite-stage P. falciparum cells were treated with ACT-213615 for increasing amount of time at IC50 concentration and cells were harvested in parralled with DMSO treated controls for microarray-based transcriptional profiling.
2012-07-19 | E-GEOD-39485 | biostudies-arrayexpress
Project description:The increasing spread of drug-resistant malaria strains underscores the need for new antimalarial agents with novel modes of action (MOAs). Here, we describe a compound representative of a new class of antimalarials. This molecule, ACT-213615, potently inhibits in vitro erythrocytic growth of all tested Plasmodium falciparum strains, irrespective of their drug resistance properties, with IC(50) values in the low single-digit nanomolar range. Like the clinically used artemisinins, the compound equally and very rapidly affects all three asexual erythrocytic parasite stages. In contrast, microarray studies suggest that the MOA of ACT-213615 is different from that of the artemisinins and other known antimalarials. ACT-213615 is orally bioavailable in mice, exhibits activity in the murine P. berghei model and efficacy comparable to that of the reference drug chloroquine in the recently established P. falciparum SCID mouse model.ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potential. Histone deacetylase (HDACs) inhibitors are being intensively pursued as potential new antimalarial drugs, and are also emerging as valuable tools for investigating transcriptional control in malaria parasites. In this study, the genome-wide transcriptional effects of three structurally related hydroxamate HDAC inhibitors were profiled in Plasmodium falciparum, the most lethal of the malaria parasite species that infects humans.
2012-07-20 | GSE39485 | GEO
Project description:Drug resistance, caused by complex and redundant mechanisms, is a major obstacle in cancer treatment, especially in liver and kidney cancers. Combinational therapy of miRNAs, which concurrently target multiple pathways, with anticancer drugs represent a new strategy to improve the drug response. By a systems approach, we identified that miR-27b, a miRNA deleted in liver and kidney cancers, sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo. Two samples transfected with nontarget miRNA control or miR-27b mimics followed by 48 hours doxorubicin treatment
2014-01-07 | E-GEOD-53872 | biostudies-arrayexpress
Project description:Drug resistance, caused by complex and redundant mechanisms, is a major obstacle in cancer treatment, especially in liver and kidney cancers. Combinational therapy of miRNAs, which concurrently target multiple pathways, with anticancer drugs represent a new strategy to improve the drug response. By a systems approach, we identified that miR-27b, a miRNA deleted in liver and kidney cancers, sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo.
2014-01-07 | GSE53872 | GEO
Project description:The development of antimalarial drug resistance is an ongoing problem threatening progress towards malaria elimination, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the devel-opment of new antimalarials with untapped targets and low propensity for resistance. In addi-tion, drug repurposing in the context of HDT can lead to a substantial decrease in the time and resources required to develop novel antimalarials. Host BCL-XL is a major target in anti-cancer therapy and is essential for the development of numerous intracellular pathogens. We hypothe-sised that red blood cell BCL-XL is essential for Plasmodium development and tested this hypoth-esis by using six BCL-XL inhibitors, including one FDA-approved compound. All BCL-xL inhibitors tested impaired proliferation of P. falciparum 3D7 parasites in vitro at low parasite inhibitory concentrations. Western blot analysis and immunofluorescence microscopy assays revealed that host BCL-xL is transferred from the host red blood cells (RBCs) to the parasite upon infection. Further, immunoprecipitation of BCL-XL coupled with mass spectrometry analysis identified that BCL-XL forms unique molecular complexes with human μ-calpain in uninfected RBCs, and with human SHOC2 in infected RBCs. These results open exciting perspectives for the development of host-directed antimalarial therapies and drug repurposing efforts.
2022-05-19 | PXD032276 | Pride
Project description:Anticancer potential of UDCA on GBM
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Project description:<p>Metabolic reprogramming in malignant cells is a hallmark of cancer that relies on augmented glycolytic metabolism to support their growth, invasion and metastasis. However, the impact of global adipose metabolism on tumor growth and the drug development by targeting adipose metabolism remain largely unexplored. Here we show that a therapeutic paradigm of drugs is effective for treating various cancer types by browning adipose tissues. Mirabegron, a clinically available drug for overactive bladders, displays potent anticancer effects in various animal cancer models, including untreatable cancers such as pancreatic ductal adenocarcinoma and hepatocellular carcinoma, via the browning of adipose tissues. Genetic deletion of the uncoupling protein 1 (UCP1), a key thermogenic protein in adipose tissues, ablates the anticancer effect. Similarly, the removal of brown adipose tissue (BAT), which is responsible for non-shivering thermogenesis, attenuates the anticancer activity of mirabegron. These findings demonstrate that mirabegron represents a paradigm of anticancer drugs with a distinct mechanism for the effective treatment of multiple cancers.</p>
2023-11-08 | MTBLS8682 | MetaboLights
Project description:Anticancer drug clustering in lung cancer based on gene expression profiles. We performed gene expression analysis in lung cancer cell lines. (used: Affymetrix GeneChip Human Genome U133 Array Set HG-U133A). We also examines the sensitivity of these cell lines to commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin, and carboplatin) via MTT assay. We related the cytoxic activity of each of these agents to corresponding expression pattern in each of the cell lines using modified NCI program. Keywords: cytotoxicity, lung cancer, anticancer drugs
2006-02-10 | GSE4127 | GEO
Project description:CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. Nine metabolites predicted to be lowered in Jurkat cells with respect to normal lymphoblasts were examined: riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole. All, alone or in combination, exhibited antiproliferative activity. Of eleven metabolites predicted to be increased or unchanged in Jurkat cells, only two (bilirubin and androsterone) exhibited significant antiproliferative activity. These results suggest that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, resulting in uninhibited cellular growth and have the implication that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery. Keywords: cell type
2008-08-04 | GSE9648 | GEO