Mulberry Leaf Extract Inhibits Invasive Potential and Downregulates Hypoxia-Inducible Factor-1α (HIF-1α) in SK-N-BE(2)C Neuroblastoma Cells

Park, Seolhyun; Kim, Yoo Sun; Lee, Hyun Ah; Lim, Yunsook; Kim, Yuri

doi:10.1271/bbb.120763

Cited by 14 publications

(9 citation statements)

References 48 publications

(50 reference statements)

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“…To investigate cell migration, wound-healing assays were performed as previously described [30]. Briefly, BE(2)C cells were grown in 6-well plates in a monolayer up to 80–90% confluence.…”

Section: Methodsmentioning

confidence: 99%

“…Cell invasion was examined in transwell invasion assays using 24-well matrigel invasion chambers (Becton Dickinson, Bedford, MA, USA) as described previously [30]. Briefly, 3 x 10 5 BE(2)C cells were seeded into the rehydrated upper wells with serum-free medium, while the lower chambers were filled with growth medium containing 5% FBS.…”

Section: Methodsmentioning

confidence: 99%

“…As previously described [30], gelatin zymography assays were conducted to analyze the enzymatic activity of MMP-2. Briefly, BE(2)C cells were grown in serum-free medium and transfected with each plasmid.…”

Section: Methodsmentioning

confidence: 99%

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Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

et al. 2017

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Neuroblastoma (NB) originates from immature neuronal cells and currently has a poor clinical outcome. NB cells possess cancer stem cells (CSCs) characteristics that facilitate the initiation of a tumor, as well as its metastasis. Human bitter taste receptors, referred to as TAS2Rs, are one of five types of basic taste receptors and they belong to a family of G-protein coupled receptors. The recent finding that taste receptors are expressed in non-gustatory tissues suggest that they mediate additional functions distinct from taste perception. While it is generally admitted that the recognition of bitter tastes may be associated with a self-defense system to prevent the ingestion of poisonous food compounds, this recognition may also serve as a disease-related function in the human body. In particular, the anti-cancer stemness and invasion effects of TAS2Rs on NB cells remain poorly understood. In the present study, endogenous expression of TAS2R8 and TAS2R10 in SK-N-BE(2)C and SH-SY5Y cells was examined. In addition, higher levels of TAS2R8 and TAS2R10 expression were investigated in more differentiated SY5Y cells. Both TAS2Rs were up-regulated following the induction of neuronal cell differentiation by retinoic acid. In addition, ectopic transfection of the two TAS2Rs induced neurite elongation in the BE(2)C cells, and down-regulated CSCs markers (including DLK1, CD133, Notch1, and Sox2), and suppressed self-renewal characteristics. In particular, TAS2RS inhibited tumorigenicity. Furthermore, when TAS2Rs was over-expressed, cell migration, cell invasion, and matrix metalloproteinases activity were inhibited. Expression levels of hypoxia-inducible factor-1α, a well-known regulator of tumor metastasis, as well as its downstream targets, vascular endothelial growth factor and glucose transporter-1, were also suppressed by TAS2Rs. Taken together, these novel findings suggest that TAS2Rs targets CSCs by suppressing cancer stemness characteristics and NB cell invasion, thereby highlighting the chemotherapeutic potential of bitter taste receptors.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

et al. 2017

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“…In this regard, several plant-derived bioactive compounds have been found to be effective in reducing HIF-1 expression and HIF-1 target gene regulation in different tumor cell types [51][52][53][54][55][56]. Below, some phytocompounds suitable to target GBM and glioma cells and their CSC fractions are described.…”

Section: The Use Of Phytocompounds To Target Cscs and Their Microenvimentioning

confidence: 99%

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

et al. 2015

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Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting.

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“…5 As documented, MLPs positively induced and activated both macrophages and neutrophils. [5][6][7][8][9][10][11][12] Dendritic cells (DCs) were first reported by Paul Langerhans in the late 19thcentury. 16 However, it was not until 1973 that Ralph M. Steinman and Zanvil A. Cohn coined the term "dendritic cell," introducing a new epoch in immunology.…”

Section: Introductionmentioning

confidence: 99%

Mulberry leaf polysaccharides modulate murine bone-marrow-derived dendritic cell maturation

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Cao³

et al. 2015

Human Vaccines & Immunotherapeutics

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Various components of mulberry leaves, such as iminosugars, flavonoids and polysaccharides, have been reported to exert anti-diabetic activity. The purpose of our present study was to examine the modulating effect of mulberry leaf polysaccharides (MLPs) on murine bone-marrow-derived dendritic cells (BMDCs). The ultrastructure, phenotype and functional maturation of BMDCs were studied using transmission electron microscopy (TEM), flow cytometry (FCM), and tested for phagocytosis, acid phosphatase (ACP) activity using an enzyme linked immunosorbent assay (ELISA). Our results demonstrated that MLPs could markedly induce BMDC maturation by up-regulating the expression of membrane phenotypic markers, such as CD80, CD86, CD83,CD40, and MHC II, down-regulating phagocytosis and ACP activity, and by enhancing the production of interleukin 12 (IL-12) and tumor necrosis factor a (TNF-a) secreted by BMDCs. We therefore concluded that MLPs can positively modulate BMDCs.

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Mulberry Leaf Extract Inhibits Invasive Potential and Downregulates Hypoxia-Inducible Factor-1α (HIF-1α) in SK-N-BE(2)C Neuroblastoma Cells

Cited by 14 publications

References 48 publications

Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

Mulberry leaf polysaccharides modulate murine bone-marrow-derived dendritic cell maturation

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