Browsing by Author "Erkisa, Merve"

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Anticancer potential of albumin bound wnt/β-catenin pathway inhibitor niclosamide in breast cancer cells
(Wiley-v C H Verlag Gmbh, 2021-08-06) Ari, Ferda; Erkisa, Merve; Pekel, Gonca; Buyukkoroglu, Gulay; Ulukaya, Engin; Erturk, Elif; ERTÜRK, ELİF; Arı, Ferda; Erkısa, Merve; Bursa Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Bursa Uludağ Üniversitesi/Sağlık Hizmetleri Meslek Yüksekokulu.; 0000-0002-6729-7908; 0000-0002-3127-742X; 0000-0002-5089-6007; 0000-0003-4875-5472; K-5792-2018; N-6551-2019; JQI-3400-2023; AAM-1001-2020; IWM-5784-2023
Albumin-based nanoparticle transport systems (nab-technology) are a new strategy in cancer treatment and we aimed to increase the effectiveness of Niclosamide using this technology. Niclosamide was bound with bovine serum albumin (BSA) by desolvation to yield nanoparticle albumin-bound Niclosamide (nab-Niclo). Nab-Niclo anticancer activity was assessed by proliferation, apoptosis and DNA damage analyses on breast cancer cells. The results implied that nab-Niclo was a more potent agent in the inhibition of cell viability than free Niclosamide and albumin. Flow cytometry analysis show that nab-Niclo triggered apoptosis by caspase and mitochondriadependent pathways in cells and nab-Niclo enhances apoptosis by induce DNA damage in cells. Overall results of this study showed that the nanoparticle form of Niclosamide is effective for breast cancer treatment, presenting a new treatment strategy that can be safe and effective for breast cancer patients.
Combination of histone deacetylase inhibitor with cu(ii) 5,5-diethylbarbiturate complex induces apoptosis in breast cancer stem cells: A promising novel approach
(Bentham Science, 2021-01-01) Erkisa, Merve; Aztopal, Nazlihan; Erturk, Elif; Ulukaya, Engin; Yilmaz, Veysel T.; Ari, Ferda; Erkisa, Merve; Aztopal, Nazlihan; YILMAZ, VEYSEL TURAN; Ari, Ferda; ARI, FERDA; ertürk; Bursa Uludağ Üniversitesi/Fen Edebiyat Fakültesi.; 0000-0002-3127-742X; 0000-0003-3118-8061; 0000-0002-2849-3332; 0000-0002-6729-7908; JQI-3400-2023; AAM-1001-2020; L-7238-2018; AAG-7012-2021; L-6687-2018
Background: Cancer Stem Cells (CSCs) are a subpopulation within the tumor that play a role in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy.Objective: In our study, we scope out the effects of a combination of a histone deacetylases inhibitor, Valproic Acid (VPA), and Cu(II) complex [Cu(barb-kappa N)( barb-kappa 2N,O)(phen-kappa N,N')]center dot H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7).Methods: The viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2',7'-dichlorofluorescein diacetate staining.Results: The VPA combined with Cu(II) complex showed anti-proliferative activity on MCF-7s cells in a dose-and time-dependent manner. Treatment with a combination of 2.5 mM VPA and 3.12 mu M Cu(II) complex induced oxidative stress in a time-dependent manner, as well as apoptosis evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels.Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy for which further analysis is required.
Development of near-infrared region luminescent N-acetyl-L-cysteine-coated Ag2S quantum dots with differential therapeutic effect
(Future Medicine, 2019-04) Buz, Pelin Turhan; Duman, Fatma Demir; Erkisa, Merve; Demirci, Gözde; Ulukaya, Engin; Acar, Havva Yağcı; Arı, Ferda; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji/Moleküler Biyoloji Bölümü.; 0000-0002-6729-7908; AAG-7012-2021; 24376085300
Aim: N-acetyl-L-cysteine (NAC) is a free radical scavenger. We developed NAC-coated Ag2S (NAC-Ag2S) quantum dot (QD) as an optical imaging and therapeutic agent. Materials & methods: QDs were synthesized in water. Their optical imaging potential and toxicity were studied in vitro. Results: NAC-Ag2S QDs have strong emission, that is tunable between 748 and 840 nm, and are stable in biologically relevant media. QDs showed significant differences both in cell internalization and toxicity in vitro. QDs were quite toxic to breast and cervical cancer cells but not to lung derived cells despite the higher uptake. NAC-Ag2S reduces reactive oxygen species (ROS) but causes cell death via DNA damage and apoptosis. Conclusion: NAC-Ag2S QDs are stable and strong signal-generating theranostic agents offering selective therapeutic effects.
Effective and new potent drug combination: Histone deacetylase and wnt/beta-catenin pathway inhibitors in lung carcinoma cells
(Wiley, 2019-09) Erkisa, Merve; Akgün, Oğuzhan; Arı, Ferda; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji, Moleküler Biyoloji Bölümü.; 0000-0002-8410-1786; 0000-0002-6729-7908; A-5608-2019; AAG-7012-2021; 57194269996; 24376085300
Lung cancer is the most commonly diagnosed cancer worldwide with a high mortality rate. In this study, the therapeutic effect of combination valproic acid and niclosamide was investigated on human lung cancer cell line. The effects of the compounds alone and combination therapy on cell viability were determined by sulforhodamine B and adenosine 5 '-triphosphate viability assays. Flow cytometry was used to determine the cell death mechanism and DNA damage levels responsible for the cytotoxic effects of combination therapy. The presence of apoptosis in cells was supported by fluorescence microscopy and also by using inhibitors of the apoptotic signaling pathway. The increase in cellular reactive oxygen species (ROS) level in combination therapy was determined by H2DCFDA staining. The effect of N-acetyl-l-cysteine combination on ROS increase was investigated on cell viability. In addition, the expression levels of the proteins associated with epigenetic regulation and cell death were analyzed by Western blotting and gene expression levels were determined using real-time quantitative polymerase chain reaction.It was observed that the combination therapy showed a cytotoxic effect on the A549 lung cancer cells compared to the individual use of the inhibitors. The absence of this effect on normal lung cells revealed the presence of a selective toxic effect. When the mechanism of cytotoxicity is examined, it has been observed that combination therapy initiates the activation of tumor necrosis receptors and causes apoptosis by activated caspase. It was also observed that this extrinsic apoptotic pathway was activated on the mitochondrial pathway. In addition, ER stress and mitochondrial membrane potential loss associated with increased ROS levels induce cell death. When the data in this study were evaluated, combination therapy caused a dramatic decrease in cell viability by inducing the extrinsic apoptotic pathway in lung cancer cell line. Therefore, it was concluded that it can be used as an effective and new treatment option for lung cancer.
Preparation and characterization of palladium derivate-loaded micelle formulation in Vitro as an Innovative therapy option against non-small cell lung cancer cells
(Wiley, 2021-08-09) Büyükköroğlu, Gülay; Şenel, Bahiye; Ulukaya, Engin; Erkisa, Merve; Arı, Ferda; Yılmaz, Veysel Turan; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-6729-7908; 0000-0002-2849-3332; 0000-0002-3127-742X; AAG-7012-2021; L-7238-2018; AAM-1001-2020; 24376085300; 56441123900; 57126208900
Nanoparticles have been used in cancer treatments to target tumor and reduce side effects. In this study, we aimed to increase the effectiveness of palladium(II) complex [PdCl(terpy)](sac) ⋅ 2H2O, which previously showed anticancer potential, by preparing the nanoparticle formulation. An inhalable micellar dispersion containing a palladium(II) complex (PdNP) was prepared and its physicochemical characteristics were evaluated using in vitro tests. Morphology, size and surface charges of particle and loading/encapsulation efficiency of PdNP were analyzed by scanning electron microscopy, zeta sizer and inductively coupled plasma mass spectrometry while aerosol properties of PdNP were measured by the next generation impactor. A549 and H1299 non-small lung cancer cell types were used for cytotoxicity using SRB and ATP assays. Fluorescent staining and M30 antigen assay were carried out for cell death evaluation. Apoptosis was confirmed by flow cytometry analyses. SEM, particle size, and zeta potential results showed the particles have inhalable properties. The amount of the palladium(II) complex loaded into the particles was quantified which indicated high encapsulation efficiencies (97 %). The micellar dispersion expected to reach the alveolar region and the brachial region was determined 35 % and 47 %, respectively. PdNP showed an anti-growth effect by increasing reactive oxygen species that is followed by the induction of mitochondria-dependent apoptosis that is evidenced by pyknotic nuclei and M30 antigen level increments and disruption of polarization of membrane in mitochondria (Δψm). The results show that PdNP might be a promising inhalable novel complex to be used in non-small cell lung cancer, which warrants animal studies in further.
Synthesis, characterization, anticancer and antioxidant activity of new nickel(II) and copper(II) flavonoid complexes
(Elsevier, 2019-07-02) Ulukaya, Engin; Alper, Pınar; Erkisa, Merve; Genckal, Hasene Mutlu; Sahin, Saliha; Ari, Ferda; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-0026-7755; 0000-0002-6729-7908; 0000-0002-3127-742X; AAH-2888-2021; AAG-7012-2021; AAM-1001-2020; AAH-2892-2021; 24376085300; 15027401600; 57212275330; 57126208900; 57197858774
Flavonoids are natural products which are known to have biological activity for human health. In this study, new mixed ligand complexes of Ni(II) and Cu(II) were synthesized by using flavonoid (quercetin or naringenin) and heterocyclic imine (2,2':6',2 ''-terpyridine or 2,2'-bipyiridine) ligands. The new complexes are [Ni(narH-1)(terpy)Cl]center dot 4H(2)O (1, nar = naringenin, terpy = 2,2':6',2 ''-terpyridine), [Cu(narH-1)(terpy)Cl]center dot H2O (2), and [Cu(queH-1)(bpy)(O3N)]center dot 1.5H(2)O (3, que = quercetin, bpy = 2,2'-bipyiridine). The structural features of the synthesized mixed ligand complexes were investigated using elemental analysis, thermogravimetric analysis, Fourier transform infrared spectroscopy, magnetic susceptibility and molar conductivity measurements. The resulting data demonstrated an octahedral geometry for Complex 1 and Complex 2 and square pyramidal geometry for Complex 3. Antioxidant capacity and total phenolic content of Complexes 1-3 were measured by the Folin-Ciocalteu and ABTS methods. Anti- proliferative effect of complexes were tested by SRB and ATP assays on MCF-7 (breast cancer), A549 (nonsmall cell lung cancer), PC-3 (prostate cancer) and HeLa (human cervical cancer) cell lines. Apoptosis was identified using by the fluorescence imaging, caspase cleaved cytokeratin-18 and flow cytometry analysis. Complex 2 and 3 had high total phenolic content and antioxidant activity. Complex 2 was found to show selective cytotoxicity through the induction of apoptosis on MCF-7 cells with having a very low IC50 value (<0.8 mu M; the half maximum inhibitory concentration) while its ligands showed much higher cytotoxicity (IC50 > 50 mu M). In conclusion, Complex 2 is a highly promising and novel compound for breast cancer and warrants further animal experiments. (C) 2019 Elsevier B.V. All rights reserved.