title: Β-carotene inhibits neuroblastoma tumorigenesis by regulating cell differentiation and cancer cell stemness.
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.
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Ji Ye
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Yoo-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Min
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: yuri.kim@ewha.ac.kr.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019207:beta Carotene
keywords: Cancer stem cells; Differentiation; Neuroblastoma; Tumorigenesis; β-Carotene