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

Stem Cell Research & Therapy
Saeed AlghamdiG Rasul Chaudhry

Abstract

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 mesenchymal stem cells (MSCs), which are important for regeneration of damaged cells and tissues, are unknown. In this study we employed umbilical cord derived MSCs as a model system to evaluate the safety of JQ1. Cord derived MSCs were treated with various doses of JQ1 and subjected to cell metabolic activity, apoptosis, and cell cycle analyses using MTT assay, Annexin-V/FITC and PI staining, and flow cytometry, respectively. The effect of JQ1 on gene expression was determined using microarray and quantitative real-time reverse transcriptase polymerase chain reaction analysis. Furthermore, protein expression of apoptotic and neuronal markers was carried out using western blot and immunostaining, respectively. Our results showed that JQ1 inhibited cell grow...Continue Reading

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Citations

Jul 30, 2016·Scientific Reports·Gwon-Soo JungKeun-Gyu Park
Oct 1, 2016·Journal of Tissue Engineering and Regenerative Medicine·Naimisha BeeravoluG Rasul Chaudhry
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Mar 31, 2018·Chemical Research in Toxicology·Yan ZhangChang Liu
Sep 15, 2021·Stem Cells·Anusree DeyHari Sharan Misra

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Datasets Mentioned

BETA
GSE705770

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
FACS
Assay
PCR
X-ray

Software Mentioned

Illumina Genome Studio
Partek Genomics Suite
SPSS
ModFit
ImageJ

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