Effects of ellagic acid in human neuroblastoma cells
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
Karlstad University Studies, ISSN 1403-8099 ; 2013:48
polyphenols, ellagic acid, neuroblastoma, SH-SY5Y cells, differentiation, proliferation, apoptosis, cell adhesion
Medical and Health Sciences
Research subject Biomedical Sciences
IdentifiersURN: urn:nbn:se:kau:diva-29905ISBN: 978-91-7063-526-7OAI: oai:DiVA.org:kau-29905DiVA: diva2:661066
2013-11-29, Ljungbergsalen, 21A 244, Universitetsgatan 2, 651 88 Karlstad, Karlstad, 10:15 (English)
Persson, Karin, Docent
Nånberg, Eewa, Professor
Artikel 4 ("Altered sensitivity...") ingick som manuskript i avhandlingen, nu publicerad.2013-11-082013-10-242016-02-24Bibliographically approved
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