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ÖZBAŞ, SUNA

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Eczacılık Fakültesi

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ÖZBAŞ

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SUNA

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Now showing 1 - 10 of 13

Open Access
A new gene therapy approach by tenascin-c genome editing induces apoptosis and cell cycle arrest in triple- negative breast cancer cells
(2023-02-01) ÖZBAŞ, SUNA; Bareke H., ŞALVA E., ÖZBAŞ S.
BACKGROUND/AIMS: There is a pressing need for new therapies for the most aggressive subtype of breast cancer, triple-negative breast cancer (TNBC). Tenascin-C (TN-C) codes for a tumor microenvironment-specific protein, which promotes apoptosis evasion and cell proliferation. The aim of this study was to knock down TN-C by using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system to induce cancer cell apoptosis and stunt cell proliferation, laying the grounds for a new gene therapy approach in TNBC.MATERIALS and METHODS: The human TNBC cell line, MDA-MB-231 cells were transfected by TN-C-specific CRISPR/Cas9 plasmids. TN-C messenger RNA levels were assessed by real-time polymerase chain reaction to determine the knock-down efficiency. Two days after the transfection, the percentage of apoptotic cells and the proportion of cells in cell cycle phases were compared between the treatment and the control groups using flow cytometry. The resultant change in cell proliferation due to the knock-down was determined by MTT assay. RESULTS: Transfection with the TN-C CRISPR/Cas9 plasmid reduced TN-C levels in the cells by approximately 49% relative to the scrambled -control CRISPR/Cas9 transfected cells. This TN-C downregulation increased the percentage of cells in apoptosis and induced G1-phase arrest. The combined effect of apoptosis and cell cycle arrest led to a significant decrease in the number of cancer cells in the treatment group.CONCLUSION: Our successful preliminary study of a potential TNBC gene therapy based on TN-C genome editing by the CRISPR/Cas9 system led to significant decrease in TNBC cell numbers and it justifies the testing of this system in more advanced preclinical studies.
Open Access
In vitro cytotoxic effect of PARP inhibitor alone and in combination with nab-paclitaxel on triple-negative and luminal A breast cancer cells
(SPANDIDOS PUBL LTD, 2018-04-12) ÖZBAŞ, SUNA; Topcul, Mehmet; Cetin, Idil; Turan, Suna Ozbas; Ozar, Melek Ozlem Kolusayin
In the present study, the in vitro cytotoxic effect of poly(ADP-ribose) polymerase (PARP) inhibitor alone and in combination with nab-paclitaxel was evaluated on human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and human luminal A breast cancer cell line MCF-7. For this purpose, cell index (CI) values obtained from xCELLigence Real-Time Cell Analysis (RTCA) DP instrument, mitotic index (MI), labelling index (LI) and apoptotic index (AI) analysis among cell kinetic parameters were used. As a result of PARP inhibitor application, there was a significant decrease in CI, MI and LI and a significant increase in AI for all the experimental groups. After application of PARP inhibitor in combination with nab-paclitaxel, the CI values were decreased for both cell lines, and the differences between the control and all the experimental groups were statistically significant (P<0.01) for all applications. PARP inhibitor, alone or in combination with nab-paclitaxel offers a promising treatment modality in different breast cancer subtypes.
Open Access
Generation of stable cell line by using chitosan as gene delivery system
(SPRINGER, 2016-08) EKENTOK ATICI, CEYDA; Salva, Emine; Turan, Suna Ozbas; Ekentok, Ceyda; Akbuga, Julide
Establishing stable cell lines are useful tools to study the function of various genes and silence or induce the expression of a gene of interest. Nonviral gene transfer is generally preferred to generate stable cell lines in the manufacturing of recombinant proteins. In this study, we aimed to establish stable recombinant HEK-293 cell lines by transfection of chitosan complexes preparing with pDNA which contain LacZ and GFP genes. Chitosan which is a cationic polymer was used as gene delivery system. Stable HEK-293 cell lines were established by transfection of cells with complexes which were prepared with chitosan and pVitro-2 plasmid vector that contains neomycin drug resistance gene, beta gal and GFP genes. The transfection efficiency was shown with GFP expression in the cells using fluorescence microscopy. Beta gal protein expression in stable cells was examined by beta-galactosidase assay as enzymatically and X-gal staining method as histochemically. Full complexation was shown in the above of 1/1 ratio in the chitosan/pDNA complexes. The highest beta-galactosidase activity was obtained with transfection of chitosan complexes. Beta gal gene expression was 15.17 ng/ml in the stable cells generated by chitosan complexes. In addition, intensive blue color was observed depending on beta gal protein expression in the stable cell line with X-gal staining. We established a stable HEK-293 cell line that can be used for recombinant protein production or gene expression studies by transfecting the gene of interest.
Open Access
Synthesis and cytotoxic activity of some 1,2,4-triazoline-3-thione and 2,5-disubstituted- 1,3,4-thiadiazole derivatives
(2010-01-01) KARAKUŞ, SEVGİ
Open Access
Plasmid DNA-loaded chitosan/TPP nanoparticles for topical gene delivery
(INFORMA HEALTHCARE, 2011-04) ÖZBAŞ, SUNA; Ozbas-Turan, Suna; Akbuga, Julide
Topical application of plasmid DNA represents an attractive route of gene delivery. Although chitosan (CS) has been widely investigated as a gene-carrier, there is very limited information about the skin application of CS-based systems for DNA. This study evaluated pDNA-loaded chitosan nanoparticles (CS-NPs) for skin gene delivery. NPs were prepared by inducing the gelation of CS upon interaction with sodium tripolyphosphate. pSV-beta-Gal was used as a reporter gene. The size, surface charge, and the other in vitro characteristics of CS-NPs were examined. Primary human dermal fibroblast cells (HDF) and mouse fibroblast NIH 3T3 cell lines (ATCC CCL-92) were used for in vitro transfection studies. In in vivo study, CS-NPs were applied to the skin of baby and adult Sprague Dawley rats by spreading on the shaved area of the back of animals. During a week animals were sacrificed and skin biopsies were taken for beta-Gal expression. beta-galactosidase enzyme activity was determined spectrophotometrically at 420 nm. The distribution of beta-galactosidase expressing cells within the skin tissue was observed by X-gal histochemical method. beta-galactosidase was continuously expressed at the nanoparticle-treated skin during the 7 days. High and continuous beta-Gal expressions were obtained with CS-NPs, although it was low in the first day. When a comparison was made between the data of baby and adult rats, markedly high transfection were measured in the skin samples of the baby rats. NPs protected pDNA against the enzyme and serum attacks. In conclusion, CS-NPs showed in vivo transfection potential in rats for skin gene delivery.
Open Access
In vitro gene silencing effect of chitosan/shRNA PDGF-D nanoparticles in breast cancer
(MARMARA UNIV, FAC PHARMACY, 2017-10-03) EKENTOK ATICI, CEYDA; Ekentok, Ceyda; Turan, Suna Ozbas; Akbuga, Julide
Breast cancer is the most common cancer worldwide in women and it is highly malignant and fatal. PDGF-D plays role in regulation of many cellular processes such as angiogenesis. PDGF-D is overexpressed in many types of cancers and promote tumor growth and metastasis. Silencing of PDGF-D gene by using shRNA with an appropriate carrier system may decrease tumor growth and metastasis. In our study, we prepared chitosan nanoparticles loaded with five different shRNA plasmids targeting different exons of PDGF-D gene. Then, nanoparticles were characterized in vitro and transfection efficiency of these nanoparticles were investigated in breast cancer cell lines (MCF7, MDA-MB-231 and MDA-MB-435). The effects of single and multiple shRNA sequences, molecular weight of chitosan (150 kDa and 400 kDa) and the amount of shRNA (100 and 500 mu g) on the characterization and transfection efficiencies of nanoparticles have been studied. Size of nanoparticles changed between 200-400 nm and approximately 95-100% encapsulation efficiency were obtained. Release of shRNA changed with the molecular weight of chitosan. It was obtained that formulation containing shRNA plasmid targeting PDGF-D exon 6 (NP1) has the highest silencing efficiency in MDA-MB-231 cell line. It was also evaluated that chitosan can be a suitable gene delivery system for shRNA targeting PDGF-D.
Open Access
Antioxidant, antimicrobial and anticarcinogenic activities of Sambucus ebulus L. flowers, fruits and leaves
(2014-02-15) BİTİŞ, LEYLA; Meriç, Zehra İlke; Bitiş, Leyla; Birteksöz Tan, Seher; Özbaş Turan, Suna; Akbuga, Jülide
Open Access
Synthesis of pro-apoptotic indapamide derivatives as anticancer agents
(TAYLOR & FRANCIS LTD, 2015-11-02) ORUN, OYA; Yilmaz, Ozgur; Turan, Suna Ozbas; Akbuga, Julide; Tiber, Pinar Mega; Orun, Oya; Supuran, Claudiu T.; Kucukguzel, S. Guniz
4-Chloro-3-({[(substitutedamino)carbonothioyl]amino} sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide (1-20) and 4-chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene]amino} sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide derivatives (21-31) were synthesized from 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide (indapamide). 4-Chloro-3-({[(4-chlorophenyl)amino)carbonothioyl]amino} sulfonyl)-N-(2-methyl- 2,3-dihydro-1H-indole-1-yl)benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA-MB-435 with 3.7% growth inhibition at the concentration of 10 mu M. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA-MB435 growth inhibition for different doses and exhibited anticancer activity with IC50 values of 85-95 mu M against melanoma cancer cell line MDA-MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC50 values ranging between 0.72 and 1.60 mu M.
Open Access
In vitro antiproliferative activity of Endemic Centaurea kilaea Boiss. against Human Tumor Cell Lines
(AVES PRESS LTD, 2015) ŞEN, ALİ; Sen, Ali; Ozbas, Suna Turan; Akbuga, Julide; Bitis, Leyla
Objective: In this study, it is aimed to determine the active extract on which substance isolation through bioactivity-guided method is to be performed in the future. Therefore, it is planned to reveal the extract exhibiting the highest antiproliferative activity by investigating the activities of heptane (CKH), chloroform (CKC), sub-fractions of active chloroform (CKCSI, CKCSII, CKCSIII) and methanol extracts (CKM) obtained from the aerial parts of Centaurea kilaea Boiss. (Asteraceae) on different cancerous cell lines. Method: Antiproliferative activity was measured against three human cancer cell lines (Hela; cervix adenocarcinoma, MCF-7; breast adenocarcinoma, PC-3; prostate adenocarcinoma) using MTT assay. Results: CKC exhibited the greatest antiproliferative activity with IC50 of 53.07; 68.64 mu g/ml against Hela and MCF-7 cells, respectively, while CKC and CKM showed the highest antitumor activity against PC-3 cell (73.92; 70.11 mu g/ml, respectively). Also, a sub-fraction II of active chloroform extract (CKCSII) demonstrated moderate antiproliferative activity with IC50 values of 60.75 and 60.70 mu g/ml against Hela and MCF-7 cells, respectively. Conclusion: The results show that CKC and CKCSII are good candidates for further bioactivity-guided fractionation in the search for new active antitumor compounds. Also, these findings confirm other results that have been reported in the literature relating to antiproliferative activities of different Centaurea species. Furthermore, active extracts would be tested on different tumor cell lines.
Open Access
In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes
(MARMARA UNIV, FAC MEDICINE, 2016-05-12) ÖZBAŞ, SUNA; Salva, Emine; Ozbas Turan, Suna; Alan, Saadet; Akbuga, Julide
The targeting of specific genes responsible from onset and progression of kidney diseases offer a new therapeutic strategy in the field of renal gene therapy. The altered expression of platelet derived growth factor (PDGF) is an important marker of renal diseases. In this study, we investigated in vitro gene silencing efficiency of chitosan nanoplexes containing PDGF-B and PDGFR-beta targeted siRNAs in the kidney cell lines including HEK-293 and MDCK and delivery to the kidney as an in vivo delivery system. As a result, PDGF-B expression was significantly inhibited by co-delivery of chitosan/siPDGF-B+siPDGFR-beta nanoplexes prepared using in the different weight ratios (10/1, 20/1 and 50/1). When 20/1 and 50/1 weight ratios of chitosan nanoplexes were i.v. injected to rats, chitosan/FITC-siPDGFB nanoplexes were reached to kidney tissue at 4 h after intravenous injection. These results suggest that delivery of siRNA using chitosan nanoplexes may be effective for the therapy of kidney diseases.