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Altered sensitivity to ellagic acid in neuroblastoma cells undergoing differentiation with 12-0-tetradecanoylphorbol-13-acetate and all-trans retinoic acid
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences.
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2015 (English)In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 76, 39-45 p.Article in journal (Refereed) Published
Abstract [en]

Ellagic acid has previously been reported to induce reduced proliferation and activation of apoptosis in several tumor cell lines including our own previous data from non-differentiated human neuroblastoma SH-SY5Y cells. The aim of this study was now to investigate if in vitro differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate or the vitamin A derivative all-trans retinoic acid altered the sensitivity to ellagic acid in SH-SY5Y cells. The methods used were cell counting and LDH-assay for evaluation of cell number and cell death, flow cytometric analysis of SubG(1)-and TUNEL-analysis for apoptosis and western blot for expression of apoptosis-associated proteins. In vitro differentiation was shown to reduce the sensitivity to ellagic acid with respect to cell detachment, loss of viability and activation of apoptosis. The protective effect was phenotype-specific and most prominent in all-trans retinoic acid-differentiated cultures. Differentiation-dependent up-regulation of Bcl-2 and integrin expression is introduced as possible protective mechanisms. The presented data also point to a positive correlation between proliferative activity and sensitivity to ellagic-acid-induced cell detachment. In conclusion, the presented data emphasize the need to consider degree of neuronal differentiation and phenotype of neuroblastoma cells when discussing a potential pharmaceutical application of ellagic acid in tumor treatment.

Place, publisher, year, edition, pages
2015. Vol. 76, 39-45 p.
Keyword [en]
Ellagic acid, Cell adhesion, Apoptosis, Neuroblastoma, Differentiation
National Category
Basic Medicine
Research subject
Biomedical Sciences
Identifiers
URN: urn:nbn:se:kau:diva-29903DOI: 10.1016/j.biopha.2015.10.008ISI: 000367541500007OAI: oai:DiVA.org:kau-29903DiVA: diva2:659187
Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2016-10-15Bibliographically approved
In thesis
1. Effects of ellagic acid in human neuroblastoma cells
Open this publication in new window or tab >>Effects of ellagic acid in human neuroblastoma cells
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A diet rich in polyphenols has been proposed to have beneficial health effects and to reduce risk of disease. Ellagic acid, a polyphenol common in red berries and pomegranates, has potential anti-tumorigenic effects that make it interesting to further study in different cancer cell systems.

Neuroblastoma is a childhood cancer that arises during development of the peripheral nervous system. Neuroblastoma, being an embryonal tumor, show loss of function of genes controlling differentiation and apoptosis. Neuroblastoma is a heterogenic tumor disease, and highly malignant neuroblastomas are difficult to treat despite different treatment modalities, identifying a need for new and combinatory treatments. A common model for human neuroblastoma is the SH-SY5Y cell line resembling immature neuroblasts that can be differentiated in vitro with several agents including the phorbol ester 12-O-tetradecanoylphorbol-13-acetate and the vitamin A-derivative all-trans retinoic acid.

Here, the effect of ellagic acid on proliferation, cell detachment and apoptosis in non-differentiated and in vitro-differentiated SH-SY5Y cells were studied with the aim of identifying cellular target mechanisms and a possible therapeutic potential for ellagic acid.

In non-differentiated cells, ellagic acid reduced cell number, inhibited cell cycle activity, and induced cell detachment and apoptosis. Apoptosis was partly mediated by the intrinsic pathway. 12-O-tetradecanoylphorbol-13-acetate and all-trans retinoic acid both induced morphological differentiation, while only the latter induced G0/G1-arrest. Single-cell analysis revealed that 12-O-tetradecanoylphorbol-13-acetate-treated cells continued cycling during neuritogenesis while these two read-outs were mutually exclusive in all-trans retinoic acid-treated cells. 12-O-tetradecanoylphorbol-13-acetate- and especially all-trans retinoic acid-differentiated cells showed lower sensitivity to ellagic acid-dependent cell detachment and apoptosis.

Place, publisher, year, edition, pages
Karlstad: Karlstads universitet, 2013. 74 p.
Series
Karlstad University Studies, ISSN 1403-8099 ; 2013:48
Keyword
polyphenols, ellagic acid, neuroblastoma, SH-SY5Y cells, differentiation, proliferation, apoptosis, cell adhesion
National Category
Medical and Health Sciences
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-29905 (URN)978-91-7063-526-7 (ISBN)
Public defence
2013-11-29, Ljungbergsalen, 21A 244, Universitetsgatan 2, 651 88 Karlstad, Karlstad, 10:15 (English)
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Note

Artikel 4 ("Altered sensitivity...") ingick som manuskript i avhandlingen, nu publicerad.

Available from: 2013-11-08 Created: 2013-10-24 Last updated: 2016-02-24Bibliographically approved

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