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Effect of ellagic acid on proliferation, cell adhesion and apoptosis in SH-SY5Y human neuroblastoma cells
Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
Karlstad University, Faculty of Technology and Science, Department of Chemistry and Biomedical Sciences.
2009 (English)In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 63, no 4, p. 254-261Article in journal (Refereed) Published
Abstract [en]

Ellagic acid, a polyphenolic compound found in berries, fruits and nuts, has been shown to possess growth-inhibiting and apoptosis promoting activities in cancer cell lines in vitro. The objective of this study was to investigate the effect of ellagic acid in human neuroblastoma SH-SY5Y cells. In cultures of SH-SY5Y cells incubated with ellagic acid, time- and concentration-dependent inhibitory effects on cell number were demonstrated.Ellagic acid induced cell detachment, decreased cell viability and induced apoptosis as measured by DNA strand breaks. Ellagic acid-induced alterations in cell cycle were also observed. Simultaneous treatment with all-trans retinoic acid did not rescue the cells from ellagic acid effects. Furthermore, the results suggested that pre-treatment with all-trans retinoic acid to induce differentiation and cell cycle arrest did not rescue the cells from ellagic acid-induced cell death.

Place, publisher, year, edition, pages
2009. Vol. 63, no 4, p. 254-261
Keywords [en]
Ellagic acid, Apoptosis, Neuroblastoma
National Category
Biological Sciences Biological Sciences
Research subject
Biomedical Sciences
Identifiers
URN: urn:nbn:se:kau:diva-9905DOI: 10.1016/j.biopha.2008.07.093OAI: oai:DiVA.org:kau-9905DiVA, id: diva2:493415
Available from: 2012-02-08 Created: 2012-02-08 Last updated: 2017-12-07Bibliographically 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. p. 74
Series
Karlstad University Studies, ISSN 1403-8099 ; 2013:48
Keywords
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)
Opponent
Supervisors
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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