title: Effect of β-carotene on cancer cell stemness and differentiation in SK-N-BE(2)C neuroblastoma cells.
abstract: Neuroblastoma is a solid tumor often diagnosed in childhood. While there have been intense efforts to develop a treatment for neuroblastoma, current therapies remain unsuccessful due to high rate of resistance and metastasis. Most cancers originate from a subset of self-renewing cells, primarily cancer stem cells (CSCs), which establish a tumor through continuous self-renewal and differentiation. The successful elimination of CSCs is an important goal in the development of effective strategies to achieve complete remission for cancers. Although β-carotene has been associated with several anticancer mechanisms, the efficacy of β-carotene against CSCs remains unclear. In the present study, β-carotene was shown to reduce cell growth and induce neuronal cell differentiation, concomitant with a marked increase in the phosphorylation of extracellular signal-regulated kinases (ERK) (p42/p44). More importantly, β-carotene inhibited self-renewal characteristics of CSCs and decreased expression of several stem cell markers. Levels of mRNA and protein of Drosophila delta-like 1 homolog (Drosophila) (DLK1) were downregulated following treatment with β-carotene. In addition, knockdown of DLK1 by siRNA enhanced the inhibitory effect of β-carotene on colony formation of neuroblastoma cells. β-carotene also potentiated the effect of cisplatin on the self-renewal characteristics of CSCs in neuroblastoma, revealing that β-carotene has the capacity to resensitize cells to cisplatin cytotoxicity by directly targeting CSCs. In conclusion, β-carotene was shown to strongly increase the anticancer efficacy against neuroblastoma cancer stem-like cells. Moreover, these results suggest that the targeting of CSCs is a novel mechanism of β-carotene. Thus, β-carotene is a potential chemotherapeutic reagent for this cancer.
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seodaemun-gu, Seoul 120-750, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Lee
authors.forename: Seolhyun
authors.initials: S
authors.lastname: Park
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
mesh_terms: D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D016501:Neurites / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C478359:WDR77 protein, human; D019207:beta Carotene; D019950:Mitogen-Activated Protein Kinase 1; D002945:Cisplatin