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    Chemical composition, antioxidant, antimicrobial and anticancer activities of endemic Cephalaria tuteliana
    (Elsevier, 2024) Kiliccioglu, Ilker; Dülger, Görkem; Senturk, Fatih; Bozyel, Mustafa Eray; Canli, Kerem; Dülger, Başaran
    Introduction: The genus Cephalaria, belonging to the Caprifoliaceae family, is a rich source of secondary metabolites, including mainly saponins which display a variety of biological activities, such as antimicrobial, antioxidant, and anticancerous effects. This study was carried out to observe the biochemical composition and to evaluate the biological activities of Cephalaria tuteliana Kus & Gokturk. Methods: The composition of endemic C. tuteliana was determined through gas chromatography-mass spectrometry (GC-MS) studies. Antimicrobial effect were determined by the disk diffusion and dilution methods for test bacteria and test fungi. The antioxidant potential of the ethanol extract was also investigated. Cell proliferation and apoptosis analysis were investigated by WST-1 and ELISA methods. The migration level of PC-3 prostate cancer cells after plant extract application was examined by wound healing assay. Also, molecular docking experiments were performed to investigate the anticancer activity of the major component found in the C.tuteliana extract. Results: GC-MS analysis showed that the predominant compounds were Phenol, 2,20-methylenebis [6-(1,1dimethyl ethyl)-4-methyl- (23.54 %), 9,12,15-octadecatrien-1-ol, (Z,Z,Z)-(6.06 %) and n-Hexadecanoic acid (3.03 %). The ethanolic extract of C. tuteliana displayed moderate antimicrobial activity against a spectrum of tested microorganisms. Also, it exhibited significant antiproliferative effects on PC-3 human prostate cancer cells while having no harmful effects on healthy control HUVEC cells. Furthermore, enhanced expressions of Caspase-3, 8, and 9 were observed in PC-3 cells after plant extract treatment. Also, cell migration level was notably reduced, especially at a dose of 400 mg/mL in PC-3 cells. The DPPH free radical scavenging activity of ethanolic extracts of C. tuteliana showed higher activity than ascorbic acid. Molecular docking experiments showed potential binding of the major aromatic compound in C.tuteliana extract to human androgen receptor 1E3G protein. Conclusion: These findings highlight the potential of C. tuteliana as a valuable natural resource and pave the way for further in vivo prostate cancer investigations. (c) 2024 SAAB. Published by Elsevier B.V. All rights reserved.
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    The Efficacy of Electrochemotherapy with Dacarbazine on Melanoma Cells
    (Mary Ann Liebert, Inc, 2024) Coskun, Alaaddin; Kayhan, Handan; Senturk, Fatih; Esmekaya, Meric Arda; Canseven, Ayse Gulnihal
    Electrochemotherapy (ECT) involves locally applying electrical pulses to permeabilize cell membranes, using electroporation (EP). This process enhances the uptake of low-permeant chemotherapeutic agents, consequently amplifying their cytotoxic effects. In melanoma treatment, dacarbazine (DTIC) is a cornerstone, but it faces limitations because of poor cell membrane penetration, necessitating the use of high doses, which, in turn, leads to increased side effects. In our study, we investigated the effects of DTIC and EP, both individually and in combination, on the melanoma cell line (SK-MEL-30) as well as human dermal fibroblasts (HDF) using in vitro assays. First, the effects of different DTIC concentrations on the viability of SK-MEL-30 and HDF cells were determined, revealing that DTIC was more effective against melanoma cells at lower concentrations, whereas its cytotoxicity at 1000 mu M was similar in both cell types. Next, an ideal electric field strength of 1500 V/cm achieved a balance between permeability (84%) and melanoma cell viability (79%), paving the way for effective ECT. The combined DTIC-EP (ECT) application reduced IC50 values by 2.2-fold in SK-MEL-30 cells and 2.7-fold in HDF cells compared with DTIC alone. In conclusion, ECT not only increased DTIC's cytotoxicity against melanoma cells but also affected healthy fibroblasts. These findings emphasize the need for cautious, targeted ECT management in melanoma therapy.
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    Fabrication of curcumin-loaded magnetic PEGylated-PLGA nanocarriers tagged with GRGDS peptide for improving anticancer activity
    (Elsevier, 2023) Senturk, Fatih; Cakmak, Soner
    Carrier-mediated drug delivery systems are highly promising as a treatment option for the targeted delivery of potent cytotoxic drugs with increased efficacy and safety. Considering that poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) polymers each provide certain advantages for biological purposes, PEGylated-PLGA nanoparticles have emerged as a leading candidate among other alternatives. Furthermore, these nanoparticles can be modified with the specific short peptide sequences such as glycine-arginine-glycine-aspartic acid -serine (GRGDS), which selectively binds to integrins overexpressed in most cancer cells, allowing for targeted delivery. Here, we reported the details in fabrication and characterization of magnetic PEGylated-PLGA nanoparticles functionalized with GRGDS peptide. In addition, superparamagnetic iron oxide nanoparticles (SPIONs) and the natural pharmaceutical compound curcumin (Cur) were loaded into these polymeric nanoparticles to assess their anticancer activity potential. Overall, this study provides comprehensive methodologies, including all synthesis procedures, challenges, and useful suggestions for peptide-conjugated polymeric nanoparticles that may be used for cellular targeting and therapeutic applications.& BULL; Step by step fabrication protocol for the Cur loaded magnetic PEGylated-PLGA nanoparticles was presented.& BULL; Validation of the fabrication and the GRGDS conjugation to the nanoparticles were shown via detailed characterization studies.& BULL; The cytotoxic effect of the Cur-loaded and GRGDS-tagged magnetic nanoparticles was tested on T98G glioblastoma cell line as a preliminary in vitro study.
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    GRGDS-conjugated and curcumin-loaded magnetic polymeric nanoparticles for the hyperthermia treatment of glioblastoma cells
    (Elsevier, 2021) Senturk, Fatih; Cakmak, Soner; Kocum, Ismail Cengiz; Gumusderelioglu, Menemse; Ozturk, Goknur Guler
    Thermally responsive and ligand-mediated drug delivery systems have the potential to improve the treatment of brain tumors, especially, most lethal one, glioblastoma multiform (GBM). Magnetic nanoparticle-mediated hyperthermia becomes one of the most promising alternative therapy for GBM treatment in cases where localized heating and targeted delivery of a therapeutic drug can be achieved on the tumor site. In this study, it is aimed to increase the therapeutic efficiency of multi-functionalized nanoparticles (NPs) in combination with radiofrequency hyperthermia (RF-HT) on GBM cells. For this purpose, firstly, a low-cost and portable home-built RFHT system suitable for in vitro/in vivo studies was successfully implemented and tested at 13.56 MHz frequency with power up to approximately 400 W. Subsequently, the highly monodispersed superparamagnetic iron oxide nanoparticles (SPIONs), which could interact with the RF magnetic field, were synthesized with the mean particle size of 5.6 +/- 0.9 nm. The obtained SPIONs were coated with poly (lactic-co-glycolic acid)-poly (ethylene glycol) di-block copolymer (PLGA-b-PEG). Most of the SPIONs were uniformly distributed in such a well-defined spherical-shaped polymeric NP. Moreover, curcumin (Cur), a potential agent for GBM treatment, was loaded into the magnetic polymeric nanoparticles (m-PNPs) with a loading capacity of 8% (w/w, Cur/NPs) and a mean diameter of Cur-loaded m-PNPs (Cur-m-PNPs) was 142 +/- 70 nm. To increase cellular uptake and targeting ability of NPs, glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide was immobilized on the Cur-m-PNPs and the amount of GRGDS was detected as 37 mu g/mg NPs. In vitro cytotoxicity studies revealed that the presence of GRGDS on Cur-m-PNPs (GRGDS-Cur-m-PNPs) improved the cytotoxic efficiency of Cur-m-PNPs by 6-fold in GBM-cells for all incubation times (24, 48 and 72 h). Furthermore, NPs with RF treatment exhibited higher antitumor activity than that of NPs without RF on GBM cells. This result may be attributed to the thermal (SPIONs) or non thermal (cellular membrane) effects or both of them on cells. Overall, this study showed that RF-HT in combination with GRGDS-Cur-m-PNPs could provide a feasible approach to improve GBM treatment.
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    A quartz crystal microbalance (QCM)-based easy setup device for real-time mass change detection under high-power RF plasma
    (Aip Publishing, 2023) Senturk, Fatih; Kocum, Ismail Cengiz; Seyitoglu, Melek Ilayda; Aksan, Eda Sevval
    Sensing technologies serve a crucial role in monitoring and testing surface properties in biosensors, thin films, and many other industries. Plasma treatments are routinely used in most of these technologies to modify the surfaces of materials. However, due to the high radio frequency (RF) noise in plasma processes, real-time surface tracking is still rather difficult. In this study, we aim to construct an easy-to-set up mass change detection system capable of operating under RF plasma conditions. For this purpose, we have presented a novel technique that utilizes the quartz crystal microbalance sensor to detect mass changes in different plasma environments. The constructed device was then tested under 13.56 MHz, 100 W plasma atmosphere. The results showed that the resonance frequency of a crystal was successfully measured with 1.0 Hz resolution under the impact of plasma-induced high power of RF noise. Moreover, as a preliminary study, we used ethylenediamine (EDA) to track changes in resonance frequency under plasma conditions and observed noise-free signals in frequency-voltage curves. Furthermore, the system's sensitivity was found to be 3.8 ng/Hz, with a test molecule (EDA) deposition of about 380 ng in the RF plasma atmosphere. Overall, this study focused on creating a relatively new approach for detecting the real-time mass change in a strong RF environment, which we believe could be an improved and easy-to-set up technique for plasma-based processes such as surface coating, etching, and activation.
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    Stepwise implementation of a low-cost and portable radiofrequency hyperthermia system for in vitro/in vivo cancer studies
    (Taylor & Francis Inc, 2021) Senturk, Fatih; Kocum, I. Cengiz; Ozturk, Goknur Guler
    In recent years, interactions of radiofrequency (RF) electromagnetic fields with biological tissue have become one of the most promising strategies for noninvasive cancer hyperthermia treatment. Despite the growing interest, there has been a scarcity of studies involving the detailed construction of a complete RF-hyperthermia (RF-HT) system. Here a low-cost and high-power RF-HT system is reported with a specific frequency which can be used in biological samples. A laboratory-constructed RF-HT system composed of a radiofrequency oscillator, radiofrequency driver, radiofrequency amplifier, radiofrequency matching network, and an induction coil applicator were constructed and characterized by a stepwise approach. Although the RF driver and amplifier were purchased as professionally designed kits, significant modifications were required for these components. The results showed that the RF-HT system was successfully constructed and tested at 13.56 MHz with a power as high as 400 W. As a preliminary biological experiment, cell culture medium exhibited an approximate 3 degrees C increase in temperature induced by the RF-HT device at 250 W for 10 min. Moreover, the developed system is suitable drug targeting, drug release, and cellular uptake and designed to be cost-effective for in vitro/in vivo studies involving cancer therapy.