| 1. |
- Fjæraa Alfredsson, Christina, et al.
(författare)
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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
- 2015
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier. - 0753-3322 .- 1950-6007. ; 76, s. 39-45
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Fjaeraa Alfredsson, Christina, et al.
(författare)
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Effect of ellagic acid on proliferation, cell adhesion and apoptosis in SH-SY5Y human neuroblastoma cells
- 2009
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier. - 0753-3322 .- 1950-6007. ; 63:4, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Fjæraa Alfredsson, Christina
(författare)
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Effects of ellagic acid in human neuroblastoma cells
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 4. |
- Fjæraa Alfredsson, Christina, et al.
(författare)
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Ellagic acid induces a dose- and time-dependent depolarization of mitochondria and activation of caspase-9 and -3 in human neuroblastoma cells
- 2014
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier. - 0753-3322 .- 1950-6007. ; 68:1, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- The polyphenol ellagic acid is found in many natural food sources and has been proposed as a candidate compound for clinical applications due to its anti-oxidative capacity and as a potential anti-tumorigenic compound. The objective of the present study was to evaluate the sensitivity to and possible apoptosis mechanism induced by ellagic acid in neuronal tumor cells. As a model the human neuroblastoma SH-SY5Y cell line was used. The methods applied were bright field and phase contrast microscopy, XTT- and LDH-assays, western blot, and flow cytometric analysis of DNA degradation and mitochondrial membrane potential. Ellagic acid treatment was found to induce a reduction in cell number preceded by alterations of the mitochondrial membrane potential and activation of caspase-9 and -3, DNA-fragmentation and cell death by apoptosis. The apoptotic cell death studied was not due to anoikis since it was significant in the adherent fraction of the cells. We conclude that ellagic acid induces dose- and time-dependent apoptosis, at least partly by the mitochondrial pathway, in an embryonal neuronal tumor cell system. This finding is in agreement with previously reported data on adult carcinoma cells thus suggesting a more general effect of ellagic acid on tumor cells.
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| 6. |
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| 7. |
- Rendel, Filip, et al.
(författare)
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Effects of Di-Isononyl Phthalate on Neuropeptide Y Expression in Differentiating Human Neuronal Cells
- 2017
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 120:3, s. 218-323
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) is an abundant neuropeptide in the mammalian brain important for behavioural consequences of stress and energy metabolism. We have addressed possible effects of the phthalate DiNP on NPY expression in human SH‐SY5Y cells, a neuronal in vitro differentiation model. Pico‐ to nanomolar doses of DiNP and its metabolite MiNP resulted in decreased NPY mRNA and peptide expression in retinoid‐differentiated cells. Thus, dys‐regulated NPY may be an adverse outcome for exposure to low doses of DiNP in human beings.
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| 8. |
- Rendel, Filip, et al.
(författare)
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RETRACTION : Effects of Di-isononyl Phthalate on Neuropeptide Y Expression in Differentiating Human Neuronal Cells (Retraction of Vol 120, Pg 318, 2017)
- 2020
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 126:1, s. 92-92
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rendel F, Alfredsson CF, Bornehag CG, Sundström BE, Nånberg E. Effects of Di‐isononyl Phthalate on Neuropeptide Y Expression in Differentiating Human Neuronal Cells, Basic & Clinical Pharmacology & Toxicology 2017, Mar;120(3):318–323 (https://onlinelibrary.wiley.com/doi/full/10.1111/bcpt.12670).The above article, published online on 13 September 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Kim Brøsen, the Nordic Association for the Publication of BCPT and John Wiley & Sons Ltd. The retraction has been agreed following an investigation into the accuracy of the data acquisition conducted by Karlstad University into the accuracy of the data acquisition, which concluded that manipulation had taken place during tests performed on an ELISA equipment in order to achieve a preferred result.
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