Retinoic acid receptor β enhanced the anti-cancer stem cells effect of β-carotene by down-regulating expression of delta-like 1 homologue in human neuroblastoma cells

Yoo Sun Kim, Eunju Kim, Yoon Jung Park, Yuri Kim

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 languageEnglish
Pages (from-to)254-260
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume480
Issue number2
DOIs
StatePublished - 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

Fingerprint

Dive into the research topics of 'Retinoic acid receptor β enhanced the anti-cancer stem cells effect of β-carotene by down-regulating expression of delta-like 1 homologue in human neuroblastoma cells'. Together they form a unique fingerprint.

Cite this