Person: ARI, FERDA
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ARI
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FERDA
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Publication Design, synthesis and anticancer activity of new benzofuran-chalcone hybrids and their water soluble sodium salts(Wiley-v C H Verlag Gmbh, 2023-03-06) Coskun, Demet; Coşkun, Mehmet Fatih; Çınar-Asa, Sibel; Akgün, Oğuzhan; Akgün, Halime; Arı, Ferda; ARI, FERDA; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0002-8410-1786; 0000-0002-2048-3252; 0000-0002-6729-7908; A-5608-2019; ADX-9980-2022; AAG-7012-2021In this study, firstly, 1-(7-ethoxy-1-benzofuran-2-yl) ethanone and 1,1'-(7-ethoxy-1-benzofuran-2,4-diyl)diethanone were synthesized for the starting reagent purposes. The synthesized benzofuran-chalcone salts were soluble in water at room temperature. Structural analysis of the synthesized compounds was characterized by elemental analysis, FT-IR and NMR spectroscopy techniques. The anticancer activities of the compounds were determined by SRB viability assay in human lung cancer (A549, H1299) and breast cancer (MCF-7, MDA-MB-231) cell lines. Findings for apoptosis were determined by flow cytometry analysis and the PARP-ELISA method. The results of the in vitro SRB analysis of the compounds showed that some of the chalcone hybrids were very effective on both types of cancer in a dose and time-dependent manner. Treatment of all cancer cell types with these hybrids resulted in a significant increase in the percentage of early and mainly late apoptotic cells, demonstrating their apoptosis-inducing effects via the Caspase 3/7 Activity.Publication 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; 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.Publication Angelica sylvestris and delphinium staphisagria extracts induces antiproliferation through caspasemediated apoptosis on human cancer cells(Inst Tecnologia Parana, 2022-01-01) Şahin, Çağatay; ÇELİKLER KASIMOĞULLARI, SERAP; Akgün, Oğuzhan; Akgün, Halime; Çelikler, Serap; ARI, FERDA; Arı, Ferda; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0002-8410-1786; 0000-0002-2048-3252; 0000-0002-4177-3478; 0000-0002-6729-7908; AAG-7012-2021; A-5608-2019; JCD-5015-2023Angelica sylvestris and Delphinium staphisagria are medicinal and aromatic herbs with a long history in medicine and food industry. In this study, we have investigated anti-cancer activity of Angelica sylvestris and Delphinium staphisagria extracts on various cell lines of lung (A549), breast (MCF-7), colon (HT-29), and cervix (HeLa) origin. Also, cytotoxicity was tested on human healthy bronchial epithelial (BEAS-2B) cells. In vitro experiments showed that plant extracts suppressed cell growth and proliferation at low concentrations by reducing cell viability on cancer cells in a time and concentration-dependent manner. It was observed that Angelica sylvestris was more effective in HT-29 and HeLa cells and Delphinium staphisagria in A549 and MCF-7 cells by suppressing cell proliferation and increasing cell death. Cell death mode (apoptosis/necrosis) was investigated via fluorescent imaging, caspase-cleaved cytokeratin 18, activated caspase-3, and cleaved-PARP (poly (ADP-ribose) polymerase). In order to evaluate the cell death mode by plant extracts apoptotic markers were investigated by fluorescence staining. Delphinium staphisagria extract (50-200 mu g/mL) caused a decrease in cell density in A549 and MCF-7 cells compared to untreated controls. A similar situation was observed in HT-29 and HeLa cell lines when treated with ASE. As a result, Delphinium staphisagria extracts induced apoptosis in A549 and MCF-7, while Angelica sylvestris extracts induced apoptosis in HT-29 and HeLa cancer cells.Publication Targeting the epithelial-mesenchymal transition (emt) pathway with combination of wnt inhibitor and chalcone complexes in lung cancer cells(Wiley, 2023-07-14) Coşkun, Demet; Arı, Ferda; ARI, FERDA; Ertürk, Elif; ERTÜRK, ELİF; Onur, Ömer E.; Akgün, Oğuzhan; Aydın, İpek; İPEK, AYDIN; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0002-8410-1786; 0000-0002-6729-7908; A-5608-2019; JQI-3400-2023; AAG-7012-2021; IUO-8513-2023Non-small cell lung cancer (NSCLC) is the most common type of the lung cancer. Despite development in treatment options in NSCLC, the overall survival ratios is still poor due to epithelial and mesenchymal transition (EMT) feature and associated metastasis event. Thereby there is a need to develop strategy to increase antitumor response against the NSCLC cells by targeting EMT pathway with combination drugs. Niclosamide and chalcone complexes are both affect cancer cell signaling pathways and therefore inhibit the EMT pathway. In this study, it was aimed to increase antitumor response and suppress EMT pathway in NSCLC cells by combining niclosamide and chalcone complexes. SRB cell viability assay was performed to investigate the anticancer activity of drugs. The drugs were tested on both NSCLC cells (A549 and H1299) and normal lung bronchial cells (BEAS-2B). Then the two drugs were combined and their effects on cancer cells were evaluated. Fluorescence imaging and enzyme-linked immunosorbent assay were performed on treated cells to observe the cell death manner. Wound healing assay, real-time quantitative polymerase chain reaction, and western blot analysis were performed to measure EMT pathway activity. Our results showed that niclosamide and chalcone complexes combination kill cancer cells more than normal lung bronchial cells. Compared to single drug administration, the combination of both drugs killed NSCLC cells more effectively by increasing apoptotic activity. In addition, the combination of niclosamide and chalcone complexes decreased multidrug resistance and EMT activity by lowering their gene expressions and protein levels. These results showed that niclosamide and chalcone complexes combination could be a new drug combination for the treatment of NSCLC.Publication Palladium (II) complex enhances ROS-dependent apoptotic effects via autophagy inhibition and disruption of multiple signaling pathways in colorectal cancer cells(Bentham Science Publ Ltd, 2021-01-01) Aydınlık, Şeyma; Erkısa, Merve; Arı, Ferda; Çelikler, Serap; Ulukaya, Engin; Aydınlık, Şeyma; ARI, FERDA; ÇELİKLER KASIMOĞULLARI, SERAP; 0000-0001-5238-2432; 0000-0002-6729-7908; 0000-0002-4177-3478; ABI-2909-2020; AAG-7012-2021; JCD-5015-2023Background: Inhibition of autophagy is reported to be a therapeutically effective strategy in overcoming resistance that is a deadly outcome in cancer. One of the most common reasons for chemo-resistance to treatment is the patients with tumors exhibiting a KRAS mutation, which occurs in approximately 40% of colorectal cancer patients.Objective: Hence, we assessed whether a Palladium (Pd)(II) complex is a promising anticancer complex, compared to 5-fluorouracil in KRAS wt HT-29 and KRAS mutant HCT-15 cells.Methods: HCT-15 and HT-29 cells were used for colorectal cancer and Chloroquine (CQ) was used as an inhibitor of autophagy. In this context, cells were treated with Pd(II) complex and 5-FU in combination with CQ for 48h and cell viability was measured by SRB assay. Cell death mode was examined with M30 and M65 ELISA assays, using annexin V/propidium iodide. Autophagy was determined by Acridine Orange (AO) staining. Furthermore, the expressions of various autophagy and apoptosis-related proteins were evaluated with Western blotting. Luminex assay and the level of Reactive Oxygen Species (ROS) were examined.Results: Cell viability was found to decrease in a dose-dependent manner and CQ enhanced cytotoxic effect in Pd(II) and 5-FU treated cells in colorectal cancer cells. Our data showed that inhibition of autophagic flux significantly increased intrinsic apoptosis through the activation of ROS. We showed that combinatorial treatment with CQ induced apoptosis via the caspase-dependent mitochondrial pathway. Luminex analysis revealed that the combination resulted in a down-regulation of NF-?B/AKT/CREB signaling pathways in both cell lines, however, decreased Erk1/2 protein expression was only observed after treatment with CQ combination in HCT-15 cells.Conclusion: We suggest that the inhibition of autophagy along with Pd(II) and 5-FU treatment has a synergistic effect on KRAS-mutant colorectal cancer cells. Autophagy inhibition by CQ promotes apoptosis via blockade of the NF-?B/AKT/CREB and activation of ROS.Publication Anti-proliferative and apoptotic effects of coordination compounds of zinc(ii), palladium(ii), and platinum(ii) with tridentate 4-(6-hydroxyphenyl)-2,6-di(thiazol-2-yl)pyridine(Wiley-v C H Verlag Gmbh, 2023-04-05) Pekdemir, Fatih; Şengül, Abdurrahman; Akgün, Oğuzhan; Acar-Selçuki, Nursel; Arı, Ferda; ARI, FERDA; Fen Edebiyat Fakültesi; Biyoloji Ana Bilim Dalı; AAG-7012-2021The mononuclear coordination compounds, [Zn(L)Cl-2] (1), [Pd(L)Cl]Cl (2), and [Pt(L)Cl]Cl (3) (L) is a tridentate-coordinated of 4-(6-hydroxyphenyl)-2,6-di(thiazol-2-yl)pyridine) were synthesized and characterized by different spectroscopic methods (FTIR, MALDI-TOF-MS, H-1 NMR, C-13 NMR, and UV/Vis). By using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, the geometrical parameters, UV/Vis absorption spectra, and infrared vibrational frequencies for the investigated compounds were explored. Anticancer activities of these compounds were determined by SRB viability assay in human lung (A549 and H1299), prostate (LNCAP), colorectal (HT-29), breast cancer (MDA-MB-231) and healthy bronchial (BEAS-2B), breast (MCF-10A), colon (CCD-18Co), and prostate (WPMY-1) epithelial cells. Caspase 3/7 activity, cleaved cytokeratin-18, and PARP levels were measured to determine apoptosis in the metal compounds found to be effective. Among the compounds, 1 showed a selective inhibiting effect and induced apoptosis on the cancer cells, thus further analyses are needed to evaluate its antitumor/anticancer activity.Publication Benzofuran substituted chalcone derivatives trigger apoptotic cell death through extrinsic pathway in human lung and breast cancer cells(Springer Int Publ Ag, 2023-07-12) Coşkun, Demet; Alioğlu, İmren; Çınar-Asa, Sibel; Arı, Ferda; ARI, FERDA; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0001-7141-6909; 0000-0002-6729-7908; AAG-7012-2021; ADX-9980-2022In this study, the anticancer potential of benzofuran-substituted chalcone derivatives Compound 1 [(3-(Benzofuran-2-yl) -5-(4-N, N-dimethylaminophenyl)-2-pyrazoline)], Compound 2 [(4) -((1E)-3-(1)-benzofuran-2-yl)-3-oxoprop-1-en-1-yl]-2-methoxyphenylchloroacetate), Compound 3 [(3-(Benzofuran-2-yl)) -5-(thiophen-2-yl)-2-pyrazoline)] and Compound 4 [3-[(1E)-3-(1-benzofuran-2-yl)-3-oxoprop-1-en-1-yl)] phenyl chloroacetate) was investigated. Their cytotoxic and apoptotic effects were explored on the human breast (MCF-7 and MDA-MB-231) and lung (A549 and H1299) cancer cells by SRB and ATP cell viability assays and Hoechst 33342/Propidium Iodide dual staining. Expressions of proteins were examined by Western blot, and cell migration test was performed for metastatic effect. In conclusion, it has been shown that Compounds 2 and 4 have high cytotoxic activity on both human breast MCF-7 (IC50:9.37-2.71) and MDA-MB-231 (IC50:5.36-2.12) and lung A549 (IC50:3.23-2.21) and H1299 (IC50:6.07-2.92) cancer cell lines respectively. In addition, it has been found that Compounds 2 and 4 induce apoptosis via extrinsic pathway in the cells. Besides, they inhibited the migration of the cells showing antimetastatic potential.Publication Effects of chalcone derived compounds on cell cycle and migration capability of human breast and lung cancer cells(Pleiades Publishing Inc, 2023-08-10) Coşkun, Demet; Arı, Ferda; ARI, FERDA; Yıldız, Y.; Avcı, H.; Altıntaş, H. Gündüz; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0002-6729-7908; AAG-7012-2021We aimed to investigate the anticancer activity of new synthesis benzofuran-substituted chalcone derivatives, which have the potential to be chemotherapeutic agents, in lung and breast cancer cell lines. The cytotoxic effect of chalcone derivatives on cell viability was determined by ATP (48 h) viability test. Doses of compounds found to be toxic to cell viability were examined using fluorescent staining (Hoechst and Propidium Iodide (PI)) to determine the mode of cell death (apoptosis and necrosis). After examining the effects of the compounds on the cell death mode, their effects on the migration abilities by the wound healing method were investigated. The effects of benzofuran chalcone derivative compounds on cell cycle were also investigated in lung and breast cancer cell lines. Two chalcone-derived compounds (Compound 1 and Compound 2) exhibited a potent anti-growth effect on lung cancer (A549 and H1299) and breast cancer (MCF-7 and MDA-MB-231) cell lines. In the double staining used to assess cell mode, the amount of PI positive cells increased with increasing dose, as did the number of pycnotic and fragmented nuclei, both of which are apoptotic markers. The compounds have been found to limit the migration capacity of cells. Finally, two chalcone-derived compounds inhibit the division of lung and breast cancer cell lines by keeping them in the G2/M phase of the cell cycle. Considering these promising results, we can say that advanced analyzes are required for the development of these two chalcone-derived chemicals as anticancer agents.Publication Toxicity assessment of hypericum olympicum subsp. olympicum l. on human lymphocytes and breast cancer cell lines(Univ South Bohemia, 2020-01-01) Balıkçı, Necmiye; Sarımahmut, Mehmet; Arı, Ferda; Aztopal, Nazlıhan; Özel, Mustafa Zafer; Ulukaya, Engin; Çelikler, Serap; Balıkçı, Necmiye; SARIMAHMUT, MEHMET; ARI, FERDA; Aztopal, Nazlıhan; Ulukaya, Engin; ÇELİKLER KASIMOĞULLARI, SERAP; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0003-2647-5875; 0000-0002-6729-7908; 0000-0003-3118-8061; 0000-0003-4875-5472; 0000-0002-4177-3478; JCN-7113-2023; AAG-7012-2021; AAV-4886-2020; K-5792-2018; L-6687-2018; JCD-5015-2023; ENX-2092-2022There is a limited number of studies about the constituents of Hypericum olympicum subsp. olympicum and its genotoxic and cytotoxic potency. We examined the possible antigenotoxic/genotoxic properties of methanolic extract of H. olympicum subsp. olympicum (HOE) on human lymphocytes by employing sister chromatid exchange, micronucleus and comet assay and analyzed its chemical composition by GCxGC-TOF/MS. The anti-growth activity against MCF-7 and MDA-MB-231 cell lines was assessed by using the ATP viability assay. Cell death mode was investigated with fluorescence staining and ELISA assays. The major components of the flower and trunk were determined as eicosane, heptacosane, 2-propen-1-ol, hexahydrofarnesyl acetone and alpha-muurolene. HOE caused significant DNA damage at selected doses (250-750 mu g/ml) while chromosomal damage was observed at higher concentrations (500 and 750 mu g/ml). HOE demonstrated anti-growth activity in a dose-dependent manner between 3.13-100 mu g/ml. Pyknotic nuclei were observed at 100 mu g/ml concentration of HOE in both cell lines. In conclusion, HOE demonstrated cytotoxic effects in a cell type-dependent manner, however its genotoxic effects were observed at relatively higher doses.Publication Identification of ALX3 gene promoter hypermethylation as a potential biomarker for lung cancer(Int Inst Anticancer Research, 2023-07-01) Kartaloğlu, Elif Beyza; Öztepe, Melih; Akgün, Oğuzhan; Acun, Tolga; Arı, Ferda; Uz-Yıldırım, Elif; Kartaloğlu, Elif Beyza; Öztepe, Melih; Akgün, Oğuzhan; ARI, FERDA; UZ YILDIRIM, ELİF; Fen Bilimleri Enstitüsü; Biyoloji Bölümü; 0000-0002-8410-1786; 0000-0002-6729-7908; AAG-7012-2021; ABY-0675-2022; JJY-2834-2023; DTJ-3797-2022; JJU-8185-2023Background/Aim: Recent studies imply the significance of promoter CpG methylation as a biomarker for various cancer types in different genes. ALX3 is one of the candidate genes with prominent promoter methylation status change. In this study, the methylation status of ALX3 gene promoter and its expression was analyzed in lung cancer cell lines and clinical samples from The Cancer Genome Atlas Program (TCGA) program. Materials and Methods: Methylation status was screened using the COBRA Assay, and gene expression in two cancer (A549 & H1299) and one normal (Beas 2B) lung cell lines was determined using RT-PCR. Results: ALX3 gene promoter was found to be hypermethylated in both lung cancer cell lines compared to normal cells. However, no difference in the expression of this gene was observed. In addition to our in vitro findings, DNA Methylation and RNA-seq data of 413 adenocarcinoma samples from TCGA-LUAD dataset were analyzed. ALX3 gene was found to be hypermethylated in tumor compared to normal samples. Interestingly, the expression level of ALX3 gene in tumors was found to be higher than that in normal samples. Conclusion: ALX3 gene promoter hypermethylation could serve as a biomarker in lung cancer.
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