Browsing by Author "Atmaca, H"

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    Anti-angiogenic effects of trabectedin (Yondelis; ET-743) on human breast cancer cells
    Atmaca, H; Uzunoglu, S
    Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate Ecteinascidia turbinata, has been shown to have antitumor effects. In this study, we assessed the possible anti-angiogenic effects of trabectedin on human umbilical vein endothelial cells (HUVECs) and breast cancer cell lines. An XTT cell viability assay was used to determine cytotoxicity. A scratch assay was used to detect the migration of cells after trabectedin treatment. Angiogenic cytokine profiles of breast cancer cell lines, before and after treatment with trabectedin, were investigated using an angiogenesis antibody array. Changes in mRNA expression levels of VEGF were evaluated using qRT-PCR. Trabectedin inhibited the viability of HUVECs and breast cancer cells in a concentration-and time-dependent manner. The migration of both HUVECs and breast cancer cells was suppressed by trabectedin treatment. Angiogenic cytokines which are known to regulate tumorigenicity and angiogenesis, such as GM-CSF, IGFBP-2, VEGF, and uPA, were inhibited, while several anti-angiogenic cytokines such as TIMP-1 and Serpin E1were induced in breast cancer cells. Furthermore, expression levels of VEGF mRNA were inhibited in all breast cancer cells tested. Although additional studies are needed to elucidate the molecular mechanisms underlying the anti-angiogenic activity of trabectedin, our results suggest that trabectedin may act as a potential anti-angiogenic agent in breast cancer cells.
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    Effect of pore architecture on the mesenchymal stem cell responses to graphene/polycaprolactone scaffolds prepared by solvent casting and robocasting
    Deliormanli, AM; Atmaca, H
    In the study graphene-containing porous, three dimensional polycaprolactone (PCL) scaffolds were prepared by solvent casting-salt leaching and robocasting methods for tissue engineering applications. Graphene nanopowders in the form of nanoflakes were incorporated into the polymer matrix at different concentrations namely 1, 3, 5 and 10 wt%. The dichloromethane was used as the solvent and sodium chloride crystals were utilized as the water-soluble porogen for the formation of an interconnected porous network (with non-oriented pores) inside the composite scaffolds in solvent casting-salt leaching method. On the other hand, acetone was utilized as solvent and PCL solutions were prepared at 20 wt% in robocasting method to construct scaffolds (with oriented pores) having a grid-like structure. The biological response of bone marrow mesenchymal stem cells seeded on these composite constructs having different architecture were tested using MTT method, live-dead cell viability assay and Alcian blue stanining. Cytotoxicity experiments revealed that mesenchymal stem cells did not show toxic response to composite robocast scaffolds. Cells proliferate and differentiate well on the surface of the robocast scaffolds compared to solvent-cast scaffolds under the same conditions. Results showed that scaffolds prepared in the study have potential to be used in cartilage tissue engineering in the presence of electric stimulation.
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    Response of mouse bone marrow mesenchymal stem cells to graphene-containing grid-like bioactive glass scaffolds produced by robocasting
    Deliormanli, AM; Türk, M; Atmaca, H
    In the study, three-dimensional, grid-like silicate-based bioactive glass scaffolds were manufactured using a robotic deposition technique. Inks were prepared by mixing 13-93 bioactive glass particles in Pluronic (R) F-127 solution. After deposition, scaffolds were dried at room temperature and sintered at 690 degrees C for 1 h. The surface of the sintered scaffolds was coated with graphene nanopowder (1, 3, 5, 10 wt%) containing poly(epsilon-caprolactone) solution. The in vitro mineralization ability of the prepared composite scaffolds was investigated in simulated body fluid. The surface of the simulated body fluid-treated scaffolds was analyzed using scanning electron microscopy to investigate the hydroxyapatite formation. Mechanical properties were tested under compression. Results revealed that graphene coating has no detrimental effect on the hydroxyapatite forming ability of the prepared glass scaffolds. On the other hand, it decreased the compression strength of the scaffolds at high graphene concentrations. The prepared grid-like bioactive glass-based composite scaffolds did not show toxic response to bone marrow mesenchymal stem cells. It was shown that stem cells seeded onto the scaffolds attached and proliferated well on the surface. Cells seeded on the scaffolds surface also demonstrated osteogenic differentiation under in vitro conditions in the absence of transforming growth factors.
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    Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines
    Atmaca, H; Bozkurt, E
    Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by -2.9, -3.7, -1.7, -1.7, -2.0 and -1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by -5.1, -2.0, -2.4, -3.1, -1.5, -2.0 and -2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer.
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    Hexagonal Boron Nitride/PCL/PLG Coatings on Borate Bioactive Glass Scaffolds for Bone Regeneration
    Ensoylu, M; Deliormanli, AM; Atmaca, H
    In this study, hexagonal boron nitride (hBN) nanoparticle- containing (0.1-2 wt%) polycaprolactone (PCL) and polylactic-co-glycolic acid (PLG)-coated 13-93B3 borate-based porous bioactive glass composite scaffolds were prepared by polymer foam replication method and their ability to use in bone tissue engineering applications was assessed. Morphological, mechanical properties, cytotoxicity and the drug release behavior of the prepared composite scaffolds were investigated. In vitro bioactivity was tested in simulated body fluid and results were analyzed using FTIR spectrometer and SEM. Results showed that both polymer coating and the existence of hBN nanoparticles in the polymeric matrix improved the compressive strength of the fabricated composite scaffolds. Incorporation of the hBN nanoparticles enhanced the in vitro hydroxyapatite forming ability of the glass composites. Results also revealed that prepared bioactive glass based composite scaffolds showed no toxicity to MC3T3-E1 cells under in vitro conditions up to 72 h and hBN-containing glass scaffolds showed higher gentamicin sulfate release rates compared to the bare polymer coated scaffolds. Manufactured bioactive glass scaffolds containing hBN nanoparticles are found to be promising for bone repair and regeneration.
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    Preparation of trivalent rare-earth element-substituted bioactive glass robocast scaffolds for osteosarcoma treatment: structural, morphological, mechanical, drug delivery, and biological properties
    Deliormanli, AM; Ensoylu, M; Atmaca, H
    In this study, trivalent rare-earth ion (Eu3+, Gd3+, and Yb3+)-substituted silicate-based bioactive glass scaffolds were prepared by robocasting method using sol-gel-derived bioactive glass powders for tissue engineering applications and cancer therapy. The structural, morphological, and mechanical properties of the prepared scaffolds as well as their in vitro bioactivity in simulated body fluid (SBF) were investigated in detail. In addition, an anticancer drug (5-FU) adsorption and release behavior of the scaffolds was studied as a function of time. In vitro, cytotoxicity and alkaline phosphatase activity were investigated using human skin fibroblast BJ and osteosarcoma SaOS-2 cells. Results showed that using lanthanide ion-containing (0.5, 1, 3, and 5 wt%) sol-gel-derived bioactive glass powders it was possible to successfully fabricate periodic, mesh-like patterned robocast glass scaffolds. All of the scaffolds prepared in the study sintered at 675 degrees C showed an amorphous structure. The compressive strength of scaffolds was in the range of 8.8 MPa to 13.6 MPa and the highest strength values were obtained in the Yb3+-containing scaffolds. Hydroxyapatite formation was obtained for the scaffolds immersed in SBF for 28 days. The fluorouracil adsorption amount was calculated to be similar to 25% for all types of scaffolds and the cumulative drug release was in the range of 20-25% depending on the dopant concentration. Results of the in vitro cell culture experiments revealed that all of the scaffolds fabricated in the study were not cytotoxic to fibroblast and osteosarcoma cells for up to 7 days under in vitro conditions. An increase was obtained for the ALP activities for both types of cells as the incubation time was increased.
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    Synthesis of silver nanoparticles using Alpinia officinarum rhizome extract induces apoptosis through down-regulating Bcl-2 in human cancer cells
    Atmaca, H; Pulat, ÇÇ; Ilhan, S
    In this study, silver nanoparticles were synthesized using Alpinia officinarum rhizome extract via an eco-friendly green synthesis method. The silver nanoparticles (AO-AgNPs) were characterized by UV-Vis spectrometry, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and dynamic light scattering. Further, the cytotoxic and apoptotic effects of AO-AgNPs were investigated in human cancer cells with different tissue origins via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometric analyses, respectively. The expression levels of anti-apoptotic Bcl-2 protein were evaluated via a real-time polymerase chain reaction. The synthesized AO-AgNPs induced a significant cytotoxic effect in all tested cancer cells but not in normal cells. AO-AgNPs induced the percentage of apoptotic cells and reduced the levels of anti-apoptotic Bcl-2 mRNA levels in cancer cells. These results demonstrate the potential application of AO-AgNPs in cancer treatment.
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    Evaluation of In Vitro Bioactivity, Cytotoxicity, and Drug Release Behavior of Er2O3 and Tb2O3-Containing Bioactive Glass Particles and Nanofibers
    Rahman, B; Deliormanli, AM; Atmaca, H
    Silicate-based bioactive glasses doped with Er3+ and Tb3+ ions (1, 3, and 5 wt%) were synthesized in the form of powders and nanofibers using sol-gel and electrospinning methods, respectively. In vitro bioactivity of the prepared powders and fibers was analyzed in simulated body fluid (SBF) for various periods, and the biological response of the osteoblastic MC3T3-E1 cells to the bioactive glass samples was studied using MTT assay and microscopic observations. The amoxicillin release behavior of the prepared glasses was examined in phosphate-buffered saline as a function of time. The results revealed that the incorporation of Er3+ and Tb3+ improved the hydroxyapatite forming ability of the prepared bioactive glass samples for up to 30 d of immersion in SBF. In vitro cytotoxicity experiments showed that Tb3+-containing glass samples were biocompatible at all concentrations; however, in the case of Er3+-containing glass particle-based samples, a decrease in cell viability was observed starting from 3 wt% Er3+. SEM observations revealed cellular adhesion and spreading on the bioactive glass scaffolds. Drug delivery experiments demonstrated that after 24 h, similar to 35 to 38% of the drug was released into the medium for both bioactive glass powder and nanofiber-based samples. Bioactive glasses synthesized in the study have the potential to be used in bone tissue engineering applications.
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    Hericium erinaceus Extract Induces Apoptosis via PI3K/AKT and RAS/MAPK Signaling Pathways in Prostate Cancer Cells
    Atmaca, H; Pulat, ÇÇ; Ilhan, S; Kalyoncu, F
    Prostate cancer (PCa) is increasing globally, surpassing lung cancer in incidence. Despite available treatment options, prostate cancer remains incurable. Hence, novel therapeutic strategies are urgently needed to treat PCa. Hericium erinaceus (HE), a medicinal mushroom, offers diverse therapeutic benefits. We examined HE's effects on PCa cells, preparing an ethanol extract and identifying its volatile compounds through GC-MS. MTT assay assessed cell viability, while specific inhibitors and western blotting explored HE's impact on PI3K/AKT and RAS/MAPK pathways. Flow cytometry and ELISA evaluated apoptosis induction. HE showed concentration- and time-dependent cytotoxicity on PCa cells with minimal effects on normal cells. Mechanistically, HE suppressed PI3K/AKT and RAS/MAPK pathways, reducing phosphorylated protein levels. Moreover, it induced PCa cell apoptosis. These findings suggest HE as a potential therapeutic for prostate cancer, shedding light on its cytotoxic and apoptotic effects for further investigation.
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    Tungsten disulfide nanoparticle-containing PCL and PLGA-coated bioactive glass composite scaffolds for bone tissue engineering applications
    Ensoylu, M; Deliormanli, AM; Atmaca, H
    In the study, tungsten disulfide (WS2) nanoparticle-containing polymer-coated bioactive glass composite scaffolds were prepared for bone tissue engineering applications. Poly-epsilon-caprolactone (PCL) and poly(D,L-lactide-co-glycolide) (PLGA) were applied on the surface of the bioactive glass scaffolds fabricated by the polymer foam replication method. Results revealed that the presence of WS2 nanoparticles (0.1 to 2 wt%) embedded in polymer matrix improved the compression strength of the prepared scaffolds and their in vitro bioactivity in simulated body fluid. Composite scaffolds did not demonstrate a cytotoxic effect on pre-osteoblastic MC3T3-E1 cells after incubation for 72 h. SEM analysis showed that cells attached to the surface of the scaffolds and spread through the interconnected porous network. Gentamicin-loaded scaffolds demonstrated a controlled drug release behavior depending on the type of polymer applied on the coating layer. The presence of WS2 nanoparticles enhanced the drug release behavior of the scaffolds. It was concluded that bioactive glass-based composites fabricated in the study have the potential to be used for bone tissue engineering purposes.
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    Effects of Galium aparine extract on the cell viability, cell cycle and cell death in breast cancer cell lines
    Atmaca, H; Bozkurt, E; Cittan, M; Tepe, HD
    Ethnopharmacological relevance: Galium species have been traditionally used for its anti-cancer, antioxidant, anti-inflammatory, antimicrobial and cardioprotective effects in the folk medicine. Galium aparine (GA) is a typical climbing plant growing widespread in Anatolia. Aim of the study: To investigate the potential anti-proliferative and apoptotic effect of GA methanol (MeOH) extract on MCF-7 and MDA-MB-231 human breast cancer cells and MCF-10A untransformed breast epithelial cells. Materials and methods: First, the extract was characterized by both liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) analyses. Then, cell viability and cell cycle distribution were investigated by XTT assay and PI staining by flow cytometry, respectively. Cell death was determined by Annexin V FITC/7-AAD staining. Results: A total of 14 major phytochemicals were identified by LC/Q-TOF/MS and 34 volatile compounds were determined by GC-MS. The extract was cytotoxic in both breast cancer cell lines in a concentration and time dependent manner and showed G1 block after 72 h extract treatment. However, it was not cytotoxic to MCF-10A breast epithelial cells. Flow cytometry analyses revealed that apoptosis was induced in MDA-MB-231 cells; however, necrosis was induced in MCF-7 cells. Conclusion: Our study suggests that GA MeOH extract may have potential anti-cancer effects against breast cancer cells without impairing normal breast epithelial cells. Ability to induction of non-apoptotic cell death besides apoptotic cell death by this complex plant-derived mixture may enable the killing of apoptosis resistant breast cancer cells but further studies should be conducted to investigate the bioavailability and metabolism of it in vivo. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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    Biological Response of Osteoblastic and Chondrogenic Cells to Graphene-Containing PCL/Bioactive Glass Bilayered Scaffolds for Osteochondral Tissue Engineering Applications
    Deliormanli, AM; Atmaca, H
    Graphene-containing 13-93 bioactive glass and poly(epsilon-caprolactone)-based bilayer, electrically conductive scaffolds were prepared for osteochondral tissue repair. Biological response of osteoblastic MC3T3-E1 and chondrogenic ATDC5 cells to the composite scaffolds was assessed under mono-culture and co-culture conditions. Cytotoxicity was investigated using MTT assay, cartilage matrix production was evaluated by Alcian blue staining, and mineralization of both types of cells in the different culture systems was observed by Alizarin red S staining. Results showed that osteoblastic and chondrogenic cells utilized in the study did not show toxic response to the prepared scaffolds under mono-culture conditions and higher cell viability rates were obtained in co-culture conditions. Larger mineralized areas were determined under co-culture conditions and calcium deposition amount significantly increased compared with that in control group samples after 21days. Additionally, the amount of glycosaminoglycans synthesized in co-culture was higher compared to mono-culture conditions. Electric stimulation applied under mono-culture conditions suppressed the viability of MC3T3-E1 cells whereas it enhanced the viability rates of ATDC5 cells. The study suggests that the designed bilayered osteochondral constructs have the potential for osteochondral defect repair.
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    Let-7a microRNA modulates caspase-3-dependent apoptosis in melanoma cells treated with dabrafenib and trametinib combination
    Keser, M; Atmaca, H
    BackgroundMalignant melanoma is an aggressive tumor with high resistance to therapy. The emergence of RAS-driven secondary cancers and BRAF-inhibitor resistance has led to the development of combination therapies targeting both BRAF and MEK.AimsThis study explored the mechanisms underlying the synergistic effects of dabrafenib (DAB) and trametinib (TM) in drug-resistant A375 and RPMI 7951 melanoma cells.MethodsCytotoxicity was assessed via MTT assay and combination effects were evaluated via combination index analysis. Apoptosis was analyzed by DNA fragmentation ELISA, while ectopic let-7a miRNA expression and inhibition were performed using lipofection. Gene expression levels were quantified by qRT-PCR, and protein expression was assessed via Western blot.ResultsThe combination of 0.7 mu M DAB and 5.0 mu M TM exhibited synergistic cytotoxicity by inhibiting the pERK1/2 signaling pathway and inducing MITF expression. This resulted in mitochondria-mediated apoptosis, characterized by a decrease in anti-apoptotic Bcl-2 and an increase in pro-apoptotic Bax, caspase-9, and caspase-3 levels. Additionally, Let-7a was identified as a crucial regulator of apoptosis sensitivity by targeting caspase-3, the key executor of apoptosis.ConclusionsThese findings provide new insights into overcoming melanoma drug resistance through combined BRAF/MEK inhibition.
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    Drug Delivery Systems for Cancer Treatment: A Review of Marine-derived Polysaccharides
    Atmaca, H; Oguz, F; Ilhan, S
    Cancer is a disease characterized by uncontrolled cell proliferation and the spread of cells to other tissues and remains one of the worldwide problems waiting to be solved. There are various treatment strategies for cancer, such as chemotherapy, surgery, radiotherapy, and immunotherapy, although it varies according to its type and stage. Many chemotherapeutic agents have limited clinical use due to lack of efficacy, off-target toxicity, metabolic instability, or poor pharmacokinetics. One possible solution to this high rate of clinical failure is to design drug delivery systems that deliver drugs in a controlled and specific manner and are not toxic to normal cells. Marine systems contain biodiversity, including components and materials that can be used in biomedical applications and therapy. Biomaterials such as chitin, chitosan, alginate, carrageenan, fucoidan, hyaluronan, agarose, and ulvan obtained from marine organisms have found use in DDSs today. These polysaccharides are biocompatible, non-toxic, biodegradable, and cost-effective, making them ideal raw materials for increasingly complex DDSs with a potentially regulated release. In this review, the contributions of polysaccharides from the marine environment to the development of anticancer drugs in DDSs will be discussed.
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    Paclitaxel in combination with AT-101 induces apoptosis via supressing Bcl-2, bcl-XL, mcl-1 proteins in human breast cancer cells.
    Cakar, B; Gursoy, P; Atmaca, H; Kisim, A; Bozkurt, E; Uzunoglu, S; Sezgin, C; Sanli, UA; Karabulut, B; Uslu, R; Karaca, B
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    FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) POLYMORPHISM STATUS OF TURKISH BREAST CANCER PATIENTS
    Uslu, R; Karaca, B; Atmaca, H; Kisim, A; Cakar, B; Karabulut, B; Sezgin, C; Uzunoglu, S
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    SYNERGISTIC EFFECT OF GOSSYPOL, A COTTON-PLANT SEED, WITH CONVENTIONAL CHEMOTHERAPEUTICS IN MCF-7 CELLS
    Karaca, B; Atmaca, H; Eniseler, AG; Unuvar-Purcu, D; Kisim, A; Karabulut, B; Uzunoglu, S; Uslu, R
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    Trabectedin to induce mitochondrial membrane potential dissipation and reactive oxygen species generation in breast cancer cells.
    Atmaca, H; Bozkurt, E; Cakar, B; Surmeli, ZG; Uzunoglu, S; Uslu, R; Karaca, B