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.
See also:
- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);
- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;
- Neuroblastoma: Complete objective response to biological treatment;
- Complete objective response to biological therapy of plurifocal breast carcinoma;