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Ege Journal of Medicine
2017, Cilt 56, Sayı 4, Sayfa(lar) 183-192
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Ellagic acid induced expression of miRNAs in breast cancer stem cells and effect of ellagic acid on apoptosis
Hasan Onur Çağlar1, Sunde Yılmaz Süslüer2, Şebnem Kavaklı3, Cumhur Gündüz2, Biray Ertürk4, Ferda Özkınay4, Ayfer Haydaroğlu5
1Ege Üniversitesi, Sağlık Bilimleri Enstitüsü, Kök Hücre Anabilim Dalı, İzmir, Türkiye
2Ege Üniversitesi Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, İzmir, Türkiye
3Ege Üniversitesi, Fen Bilimleri Enstitüsü, Biyoteknoloji Anabilim Dalı, İzmir, Türkiye
4Ege Üniversitesi Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İzmir, Türkiye
5Ege Üniversitesi Tıp Fakültesi, Radyasyon Onkolojisi Anabilim Dalı, İzmir, Türkiye
Keywords: Ellagic acid, breast cancer stem cells, miRNAs, apoptosis

Aim: miRNAs which are associated with estrogen dependent tumorigenesis of breast cancer are suppressed by ellagic acid (EA) treatment. However, modulation of expression profiles of miRNAs in breast cancer stem cells (BCSCs) after EA treatment is still unclear. In this study, it was aimed to show EA-induced apoptosis in BCSCs and to determine altered expression profiles of miRNAs after EA treatment.

Materials and Methods: Cytotoxic effects of EA on BCSCs were examined by WST-1 reagent test. Apoptosis and cell cycle analysis after EA treatment were detected by flow cytometry analysis. After EA treatment, miRNA expression profiles of BCSCs were determined by RT-PCR miRNA array.

Results: Cytotoxic effect of EA on BCSCs was found. IC50 concentration of EA at 48th and 72nd hours was 24.8 μM. EA did not induce apoptosis in BCSCs. In addition, S phase arrest was observed at 24th, 48th, 72nd hours of EA treatment. Expression profiles of 76 of totally 84 miRNA genes were detected. Expression of hsa-miR-125b-1-3p was increased as 3.59 folds by EA treatment. Expression profiles of all the others miRNAs, including members of Let-7 and miR-200 families, showed a decrease due to EA treatment.

Conclusion: In this study, it was observed that EA leads to upregulated expression of hsa-miR-125b-1-3p in contrast to downregulated expression of all other miRNAs, especially hsa-miR-485-5p and hsa-miR-328-3p, and does not induce apoptosis in BCSCs. It was suggested that BCSCs may show resistance to EA treatment due to aberrant expression profiles of miRNAs.


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