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β‐carotene inhibits neuroblastoma tumorigenesis by regulating cell differentiation and cancer stem cell stemness (LB400)
Author(s) -
Lim Ji Ye,
Kim YooSun,
Kim KyungMi,
Min SooJin,
Kim Yuri
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb400
Subject(s) - cancer research , cancer stem cell , carcinogenesis , vimentin , stem cell , cellular differentiation , cancer , neuroblastoma , tumor initiation , cancer cell , differentiation therapy , biology , chemistry , microbiology and biotechnology , medicine , immunology , cell culture , biochemistry , immunohistochemistry , genetics , gene , acute promyelocytic leukemia , retinoic acid
Neuroblastoma (NB) is the most common extracranial solid cancer in young children and malignant NB cells possess cancer stem cells (CSCs) characteristics. The successful elimination of CSCs is a good strategy for developing effective preventive and chemotherapeutic agent. CSCs possess characteristics, including differentiation and turmorigenicity. Although β‐carotene has been associated with many anticancer mechanisms, there is the lack of evidence in the efficacy β‐carotene on CSCs. In the present study, we investigated the effects of β‐carotene on tumor cell differentiation and tumorigenicity using xenograft model which were injected with SK‐N‐BE(2)C NB cells subcutaneously. We found that β‐carotene supplementation significantly inhibited tumor incidence as well as growth compared to tumor control. Furthermore, β‐carotene was shown to induce tumor cell differentiation by up‐regulating vimentin, peripherin, and neurofilament expression. On the other hand, β‐carotene significantly suppressed tumor stemness by down‐regulating CSCs markers such as Oct3/4 and DLK1 expression. It has been reported that the increased expression of hypoxia‐inducible factor1‐α (HIF1‐α) is associated with cancer stemness. Our result has shown that β‐carotene treatment significantly down‐regulated HIF1‐α expression and its downstream target, vascular endothelial growth factor (VEGF). Taken together, these results suggest β‐carotene has chemotherapeutic effects on NB cells by regulating cell differentiation and CSCs stemness. Grant Funding Source : This research was supported by the National Research Foundation of Korea (Project No. 2011‐0008169) and Brain Korea 21 plus project (Project No. 22A20130012143).