β-Carotene inhibits neuroblastoma tumorigenesis by regulating cell differentiation and cancer cell stemness

Ji Ye Lim, Yoo Sun Kim, Kyung Mi Kim, Soo Jin Min, Yuri Kim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Neuroblastoma (NB) is the most common extracranial solid cancer in young children and malignant NB cells have been shown to possess cancer stem cell (CSC) characteristics. Thus, the successful elimination of CSCs represents a strategy for developing an effective preventive and chemotherapeutic agent. CSCs are characterized by differentiation and tumorigenicity. β-Carotene (BC) has been associated with many anticancer mechanisms, although the efficacy of BC on CSCs remains unclear. In the present study, the effects of BC on tumor cell differentiation and tumorigenicity was investigated using a xenograft model. Mice were pretreated with BC for 21 days, then received a subcutaneous injection of SK-N-BE(2)C cells. Both tumor incidence and tumor growth were significantly inhibited for mice that received BC supplementation compared to the control group. Treatment with BC has also been shown to induce tumor cell differentiation by up-regulating differentiation markers, such as vimentin, peripherin, and neurofilament. Conversely, BC treatment has been shown to significantly suppress tumor stemness by down-regulating CSC markers such as Oct 3/4 and DLK1. BC treatment also significantly down-regulated HIF1-α expression and its downstream target, vascular endothelial growth factor (VEGF). Taken together, these results suggest that BC is a potential chemotherapeutic reagent for the treatment of NB, and mediates this effect by regulating the differentiation and stemness of CSCs, respectively.

Original languageEnglish
Pages (from-to)1475-1480
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number4
DOIs
StatePublished - 8 Aug 2014

Keywords

  • Cancer stem cells
  • Differentiation
  • Neuroblastoma
  • Tumorigenesis
  • β-Carotene

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