Abstract
Neuroblastoma (NB) is childhood malignancy that retains characteristics of cancer stem cells (CSCs). Targeting the CSCs is one of the therapeutic strategies proposed to achieve complete remission of NB. β-carotene (BC), an active precursor of retinoids, is a well-known antioxidant reported to possess anti-CSCs effects. Here, we investigated the involvement of retinoic acid receptors (RARs) in the anti-CSCs effects of BC. Treatment with BC or retinoic acid (RA) upregulated RARβ mRNA expression in two NB cell lines. Inhibition of RARβ using siRNA up-regulated gene expression of delta-like 1 homologue (DLK1), a marker of CSCs. To understand the molecular mechanisms of RARβ-mediated inhibition of DLK1, four retinoic acid receptor elements (RAREs) were identified in the promoter of DLK1. Chromatin immunoprecipitation assays indicated that RARβ bound directly to a RARE in the DLK1 promoter region. Knock-down of RARβ also increased the self-renewal capacity of NB cells, which was suppressed by BC. Taken together, this study provided evidence that the therapeutic anti-CSC effects of BC depend on RARβ and its ability to interact with and down-regulate the CSCs marker, DLK1.
Original language | English |
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Pages (from-to) | 254-260 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 480 |
Issue number | 2 |
DOIs | |
State | Published - 11 Nov 2016 |
Bibliographical note
Funding Information:This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( NRF-2014R1A1A2056341 ), Brain Korea 21 Plus (Project Number: 22A20130012143), and the Ewha Womans University scholarship of 2015.
Publisher Copyright:
© 2016 Elsevier Inc.
Keywords
- Cancer stem cells
- DLK1
- Neuroblastoma
- Retinoic acid β
- β-carotene