Unknown,Transcriptomics,Genomics,Proteomics

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BET Protein Inhibitor JQ1 Induces Cell Cycle Arrest in Mesenchymal Stem Cells


ABSTRACT: Efficacy and safety of anticancer drugs are traditionally studied using cancer cell lines and animal models. Recently, a potential anticancer agent, JQ1, an inhibitor of bromodomain and extra terminal (BET) protein, has been shown to promote apoptosis of cancerous cells by arresting them in G1 phase of the cell cycle. However, the effect of JQ1 on normal cells is poorly understood. In this study, we investigated the safety of JQ1 by using human umbilical cord mesenchymal stem cells (MSCs) as an in vitro model system. Our results indicated that JQ1 induced cell cycle arrest in G1 phase of MSCs, but did not promote apoptosis. Microarray analysis of MSCs treated with JQ1 indicated that it down-regulated genes involved not only in cell cycle regulation but also DNA replication, mitosis, and cell division. Although many studies have suggested the potential of JQ1 as an anticancer agent, our findings suggest that it caused a deleterious effect on normal cells and may not be safe for anticancer therapy. Human umbilical cord derived MSCs were cultured in vitro and treated with either 100 nM or 500 nM JQ1 for 24 hrs. Gene expression of treated cells was compared to untreated cultured cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Bryan Thibodeau 

PROVIDER: E-GEOD-70577 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

BET protein inhibitor JQ1 inhibits growth and modulates WNT signaling in mesenchymal stem cells.

Alghamdi Saeed S   Khan Irfan I   Beeravolu Naimisha N   McKee Christina C   Thibodeau Bryan B   Wilson George G   Chaudhry G Rasul GR  

Stem cell research & therapy 20160201


<h4>Background</h4>Efficacy and safety of anticancer drugs are traditionally studied using cancer cell lines and animal models. The thienodiazepine class of BET inhibitors, such as JQ1, has been extensively studied for the potential treatment of hematological malignancies and several small molecules belonging to this class are currently under clinical investigation. While these compounds are well known to inhibit cancer cell growth and cause apoptosis, their effects on stem cells, particularly m  ...[more]

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