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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
Biomedical Sciences, Department of Health Sciences, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.
Biomedical Sciences, Department of Health Sciences, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.
Biomedical Sciences, Department of Health Sciences, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.
Biomedical Sciences, Department of Health Sciences, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.ORCID iD: 0000-0001-9302-2396
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2015 (English)In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 76, p. 39-45Article 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
Elsevier, 2015. Vol. 76, p. 39-45
Keywords [en]
Ellagic acid, Cell adhesion, Apoptosis, Neuroblastoma, Differentiation
National Category
Basic Medicine Cell and Molecular Biology
Research subject
Biomedical Sciences
Identifiers
URN: urn:nbn:se:oru:diva-79030DOI: 10.1016/j.biopha.2015.10.008ISI: 000367541500007PubMedID: 26653548Scopus ID: 2-s2.0-84949206850OAI: oai:DiVA.org:oru-79030DiVA, id: diva2:1386341
Funder
The Royal Swedish Academy of Sciences
Note

This work was financially supported by The County Council of Värmland, The Swedish Childrens Cancer Society and The Royal Swedish Academy of Sciences.

Available from: 2013-10-24 Created: 2020-01-17 Last updated: 2020-01-27Bibliographically approved

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Fjæraa Alfredsson, ChristinaRendel, FilipSundström, Birgitta ENånberg, Eewa

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