Kişi: ARI, FERDA
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Yayın Sadece Metadata Epigenetic modulators combination with chemotherapy in breast cancer cells(Wiley, 2021-02-20) Arı, Ferda; Napieralski, Rudolf; Akgün, Oğuzhan; Magdolen, Viktor; Ulukaya, Engin; ARI, FERDA; Akgün, Oğuzhan; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü; 0000-0002-6729-7908; 0000-0002-8410-1786; A-5608-2019; AAG-7012-2021Despite the concerning adverse effects on tumour development, epigenetic drugs are very promising in cancer treatment. The aim of this study was to compare the differential effects of standard chemotherapy regimens (FEC: 5-fluorouracil plus epirubicine plus cyclophosphamide) in combination with epigenetic modulators (decitabine, valproic acid): (a) on gene methylation levels of selected tumour biomarkers (LINE-1, uPA, PAI-1, DAPK); (b) their expression status (uPA and PAI-1); (c) differentiation status (5meC and H3K27me3). Furthermore, cell survival as well as changes concerning the invasion capacity were monitored in cell culture models of breast cancer (MCF-7, MDA-MB-231). A significant overall decrease of cell survival was observed in the FEC-containing combination therapies for both cell lines. Methylation results showed a general tendency towards increased demethylation of the uPA and PAI-1 gene promoters for the MCF-7 cells, as well as the proapoptotic DAPK gene in the treatment regimens for both cell lines. The uPA and PAI-1 antigen levels were mainly increased in the supernatant of FEC-only treated MDA-MB-231 cells. DAC-only treatment induced an increase of secreted uPA protein in MCF-7 cell culture, while most of the VPA-containing regimens also induced uPA and PAI-1 expression in MCF-7 cell fractions. Epigenetically active substances can also induce a re-differentiation in tumour cells, as shown by 5meC, H3K27me3 applying ICC.Significance of the study Epigenetic modulators especially in the highly undifferentiated and highly malignant MDA-MB-231 tumour cells significantly reduced tumour malignancy thus; further clinical studies applying specific combination therapies with epigenetic modulators may be warranted.Yayın Açık Erişim Investigation of the efficacy of paclitaxel on some miRNAs profiles in breast cancer stem cells(Tübitak Bilimsel ve Teknolojik Araştırma Kurumu, 2021-01-01) Ertürk, Elif; Arı, Ferda; Akgün, Oguzhan; Ulukaya, Engin; Küçükali, Cem İsmail; Zeybek, Ümit; ERTÜRK, ELİF; ARI, FERDA; Akgün, Oguzhan; 0000-0002-6729-7908; 0000-0002-8410-1786; 0000-0003-4875-5472; 0000-0001-9851-8577; A-5608-2019; K-5792-2018; JQI-3400-2023Understanding of the functions of microRNAs in breast cancer and breast cancer stem cells have been a hope for the development of new molecular targeted therapies. Here, it is aimed to investigate the differences in the expression levels of let-7a, miR-10b, miR-21, miR-125b, miR-145, miR-155, miR-200c, miR-221, miR-222 and miR-335, which associated with gene and proteins in MCF-7 (parental) and MCF-7s (Mammosphere/stem cell-enriched population/CD44+/CD24-cells) cells treated with paclitaxel. MCF7-s were obtained from parental MCF-7 cells. Cytotoxic activity of paclitaxel was determined by ATP assay. Total RNA isolation and cDNA conversion were performed from the samples. Changes in expression levels of miRNAs were examined by RT-qPCR. Identified target genes and proteins of miRNAs were analyzed with RT-qPCR and western blot analysis, respectively. miR-125b was significantly expressed (2.0946-fold; p = 0.021) in MCF-7s cells compared to control after treatment with paclitaxel. Downregulation of SMO, STAT3, NANOG, OCT4, SOX2, ERBB2 and ERBB3 and upregulation of TP53 genes were significant after 48 h treatment in MCF-7s cells. Protein expressions of SOX2, OCT4, SMAD4, SOX2 and OCT4 also decreased. Paclitaxel induces miR-125b expression in MCF-7s cells. Upregulation of miR-125b may be used as a biomarker for the prediction of response to paclitaxel treatment in breast cancer.Yayın Sadece Metadata Soloxolone methyl, as a 18βH-glycyrrhetinic acid derivate, may result in endoplasmic reticulum stress to induce apoptosis in breast cancer cells(Elsevier, 2021-01-15) Alper, Pınar; Salomatina, Oksana, V; Salakhutdinov, Nariman F.; Ulukaya, Engin; Arı, Ferda; Alper, Pınar; ARI, FERDA; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü; 0000-0001-9631-3551; 0000-0002-6729-7908; DUL-1586-2022; AAG-7012-2021Being one of the leading causes of cancer death among women, various chemotherapeutic agents isolated from natural compounds are used in breast cancer treatment and consequently studies to develop new drugs still continue. There are several studies on 18 beta H-glycyrrhetinic acid, a secondary metabolite which is found in Glycyrrhiza glabra (liquorice roots), as a potential anticancer agent. In this study, the cytotoxic and apoptotic effects of Soloxolone methyl compound, a semisynthetic derivative of 18 beta H-glycyrrhetinic acid were investigated on breast cancer cells (MCF-7, MDA-MBA-231). Soloxolone methyl is found to be cytotoxic on both MCF-7 and MDA-MBA-231 breast cancer cells by inducing apoptosis. Especially in MDA-MB-231 cells apoptosis is detected to be triggered by ER stress. The antigrowth effects of Soloxolone methyl were determined using MTT and ATP assays. To identify the mode of cell death (apoptosis/necrosis), fluorescent staining (Hoechst 33342 and Propidium iodide) and caspase-cleaved cytokeratin 18 (M30-antigen) analyses were used. In addition, apoptosis was investigated on gene and protein levels by PCR and Western Blotting. Soloxolone methyl decreased cell viability on cells in a dose and time-dependent manner and induced apoptosis markers. An increase on apoptotic proteins related to endoplasmic reticulum stress (IRE1-alpha, Bip, CHOP) was also determined in MDA-MB-231 cells. Moreover, an increase of apoptotic gene expressions was determined in both cells treated with Soloxolone methyl. Advance analyses should be performed to elucidate the potential of Soloxolone methyl as an anticancer agent in breast cancer treatment.