Browsing by Author "Ozdemir, Ozlem"

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Anticancer Effects of Novel NSAIDs Derivatives on Cultured Human Glioblastoma Cells
(Walter de Gruyter GmbH, 2021) Ozdemir, Ozlem; Marinelli, Lisa; Cacciatore, Ivana; Ciulla, Michele; Emsen, Bugrahan; Di Stefano, Antonio; Turkez, Hasan
Several epidemiologic, clinical and experimental reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) could have a potential as anticancer agents. The aim of this study was the evaluation of cytotoxic potential in human glioblastoma cells of novel synthesized NSAID derivatives, obtained by linking, through a spacer, alpha-lipoic acid (ALA) to anti-inflammatory drugs, such as naproxen (AL-3, 11 and 17), flurbiprofen (AL-6, 13 and 19) and ibuprofen (AL-9, 15 and 21). The effects on the level of gene expression were also determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. According to our results, NSAID derivatives exhibited concentration dependent cytotoxic effects on U87-MG cell line when compared with the control group. Moreover, treatment of the most active compounds (AL-3, AL-6 and AL-9) caused upregulation of tumor suppressor gene PTEN and downregulation of some oncogenes such as AKT1, RAF1 and EGFR. In conclusion, our results revealed that AL-3, AL-6 and AL-9 could be suitable candidates for further investigation to develop new pharmacological strategies for the prevention of cancer.
Antioxidant and Anticancer Activities of Extract of Inula Helenium (L.) in Human U-87 Mg Glioblastoma Cell Line
(Wolters Kluwer Medknow Publications, 2018) Koc, Kubra; Ozdemir, Ozlem; Ozdemir, Aysenur; Dogru, Unsal; Turkez, Hasan
Aims: The aim of this study is to explore the antioxidant and antiproliferative activities of aqueous extract from aerial parts of Inula helenium (L.) against human U-87 MG glioma cell line. Materials and Methods: The 3' -(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays were used to study antiproliferative and cytotoxic activities against U-87 MG cell after 48 h exposure. In addition, to assess the oxidative effects, total antioxidant capacity and total oxidant status levels were also measured. Results: Finally, the aqueous extracts displayed antiproliferative and cytotoxic activities at high concentrations tested, particularly at 200 mu g/ml, without causing to oxidative stress. Conclusion: The results strengthen the evidence that I. helenium could be considered a natural resource of potential antitumor agents for brain cancer. In addition, this study is expected to expand the existing information on the anticancer activity of I. helenium and to assist in a more focused design of further research as chemotherapeutic agents.
A Caryophyllene Oxide and Other Potential Anticholinesterase and Anticancer Agent in Salvia Verticillatasubsp. Amasiaca (Freyn & Bornm.) Bornm. (Lamiaceae)
(Taylor & Francis Inc, 2020) Karakaya, Songul; Yilmaz, Serdar Volkan; Ozdemir, Ozlem; Koca, Mehmet; Pinar, Nur Munevver; Demirci, Betul; Baser, K. Husnu Can
In vitro cholinesterase inhibition, antioxidant and anticancer potentials of the essential oils and extracts of flowers and aerial parts of Salvia verticillata subsp. amasiaca have been studied. The GC-MS and GC-FID analyses found that major components of the essential oils were caryophyllene oxide, caryophylladienol II, spathulenol, hexahydrofarnesyl acetone and phytol. Oxygenated sesquiterpenes and sesquiterpene hydrocarbons were identified in the essential oils as the dominating groups of compounds. Caryophyllene oxide indicated strong cholinesterase inhibitory activities and antioxidant effect. The essential oil from aerial parts exhibited high anticancer activity on U-87 MG and PC-3 cells with 0% and 45.56% cell viability, respectively. Microscopic analysis of different parts of the experimental plant revealed that glandular trichomes of flowers contain more oxygenated sesquiterpene hydrocarbons, while glandular trichomes of the aerial parts contain monoterpene hydrocarbons. It was confirmed that S. verticillata subsp. amasiaca had similar kinds of capitate and peltate trichomes like other Salvia members.
Cytotoxic Activity of the Aqueous Extract of Micromeria Fruticosa (L.) Druce Subsp Serpyllifolia on Human U-87 Mg Cell Lines
(Institute of Biological Research Sinisa Stankovic, 2017) Koc, Kubra; Ozdemir, Ozlem; Kizilkaya, Omer Faruk; Sengul, Meryem; Turkez, Hasan
Micromeria fruticosa (L.) Druce subsp. serpyllifolia, which is widely used in folk medicine as a medicinal herbal tea, is grown in different areas of Turkey and the Mediterranean region. The present study was conducted to evaluate the aqueous extract of Micromeria fruticosa subsp. serpyllifolia for its antioxidant and antiproliferative activity on a human glioblastoma multiforme cell line (U-87 MG), which has not been reported before. Here, the extract was added to cultures at 8 different concentrations (0-200 mu g/mL). Cell viability and cell membrane damage was determined using the MTT and LDH assays for 48 h, respectively. To examine the oxidative effects, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were measured. The extract displayed considerable antiproliferative activities at the high concentrations of 175 and 200 mu g/mL. Furthermore, the extract caused a significant increase in the release of the lactate dehydrogenase (LDH) enzyme in a concentration-dependent manner; 200 mu g/mL of extract enhanced the release of LDH. Treatments with extract at higher doses increased TOS levels and decreased TAC levels in human U-87 MG cells. Our study suggests that the aqueous extract of Micromeria fruticosa ssp. serpyllifolia was capable of inducing growth inhibition of cancer cells. These results encourage further research to assess the value of the extract in modern phytotherapy.
Cytotoxic and Antioxidant Properties of Essential Oil of Centaurea Behen L. in Vitro
(Springer, 2019) Celikezen, Fatih Caglar; Hayta, Sukru; Ozdemir, Ozlem; Turkez, Hasan
Centaurea species of Asteraceae family are widely use in traditional medicine. Despite wide medicinal use of Centaurea sp., there is limited knowledge concerning Centaurea behen toxicity. Therefore, in this study, it is aimed to determine cytotoxic and oxidative effects of essential oil of C. behen on human blood cell cultures. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays were performed to determine cytotoxic effects. In addition, total antioxidant capacity (TAC) and total oxidative status (TOS) were examined to determine oxidative potentials. The results indicated that all tested concentrations of essential oil of C. behen were cytotoxic and led to decreases of cell viability in both assays. Besides, C. behen led to significant increases of TOS levels and decreases of TAC levels. As a conclusion, the present study showed for the first time the cytotoxic and oxidant effects of essential oil of C. behen on cultured human whole blood cells.
Cytotoxic Effect and Molecular Docking Studies of Essential Oils Ofcymbocarpum Erythraeum (Dc.) Boiss. (Apiaceae) as Potential Inhibitors of Cholinesterase
(Taylor & Francis Inc, 2020) Karakaya, Songul; Ozdemir, Ozlem; Koca, Mehmet; Demirci, Betul; Aksakal, Ozkan; Turkez, Hasan; Baser, K. Husnu Can
This investigation displays antioxidant potential ofCymbocarpum erythraeumessential oils and their biological effects like cytotoxic and anticholinesterase. The antioxidant capacities of the essential oils were estimated by DPPH, TBA, TOS assays. The anticholinesterase activity of essential oils was estimated utilizing Ellman method. The human U-87MG and PC-3 were handled and measurements were estimated by MTT test. The root essential oil showed high cytotoxic activity on PC-3 cells with 48.33% whereas aerial part essential oils indicated high cytotoxic activity on U-87MG cells with 34.62% at 0.03 mg/L. Root oil presented the highest acetylcholinesterase and butyrylcholinesterase inhibition (IC50: 113, 197 mu M, respectively). The GC-FID and GC-MS assays showed that major components of aerial part with flowers and root oils were (E)-2-decenal (52.1%); (E)-2-dodecenal (36.1%), and (E)-2-tetradecenal (22.3%), respectively. (E)-2-dodecenal was a major compound of root il and exhibited AChE and BuChE inhibitory (IC50: 100, 136 mu M, respectively) and antioxidant effects.
Genotoxicity Testing: Progress and Prospects for the Next Decade
(Taylor & Francis Ltd, 2017) Turkez, Hasan; Arslan, Mehmet E.; Ozdemir, Ozlem
Introduction: Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes.Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages. The limitations that have arisen as a result of the common use of these methods were also discussed. Finally, the perspectives of further prospects on the use of genotoxicity testing and genotoxic mode of action were emphasized.Expert opinion: The solution of actual and practical problems of genetic toxicology is inarguably based on the understanding of DNA damage mechanisms at molecular, subcellular, cellular, organ, system and organism levels. Current strategies to investigate human health risks should be modified to increase their performance for more reliable results and also new techniques such as toxicogenomics, epigenomics and single cell approaches must be integrated into genetic safety evolutions. The explored new biomarkers by the omic techniques will provide forceful genotoxicity assessment to reduce the cancer risk.
In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells
(MDPI, 2022) Arslan, Mehmet Enes; Tatar, Arzu; Yildirim, Ozge Caglar; Sahin, Irfan Oguz; Ozdemir, Ozlem; Sonmez, Erdal; Turkez, Hasan
Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC >= 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.
Inhibition of Growth of U87mg Human Glioblastoma Cells by Usnea Longissima Ach
(Acad Brasileira de Ciências, 2019) Emsen, Bugrahan; Ozdemir, Ozlem; Engin, Tubanur; Togar, Basak; Cavusoglu, Seyda; Turkez, Hasan
Herbal medicines are efficient to reduce side effects in the fight against glioblastoma, which plays a critical role within brain cancer species. The recent studies designated for testing the effects of lichens that have shown numerous anticancer activities on glioblastoma so far. In the present study, different concentrations of water extract obtained from Usnea longissima Ach. were used in order to determine cytotoxic (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests), antioxidant (via total antioxidant capacity test), pro-oxidant (via total oxidant status test) and genotoxic (via 8-hydroxy-2'-deoxyguanosine test) effects of them on human U87MG-glioblastoma cancer cell lines. Primary mixed glial-neuronal non-cancerous cells from Sprague-Dawley rats were also utilized to measure the effects of treatments on non-cancerous cells. Based on median inhibitory concentration values, the data belonged to non-cancerous cells (2486.71 mg/L) showed distinct towering compared to U87MG (80.93 mg/L) cells. The viability of non-cancerous and U87MG cells exposed to extract is decreased in a dose dependent manner. It was also showed that low concentrations of extract notably increased total antioxidant capacity on non-cancerous cells. In addition, various phenolic compounds in extract were detected through high-perfonnance liquid chromatography. The recent results encourage that extract will be able to have therapeutic potential against glioblastoma.
Memantine-Derived Drugs as Potential Antitumor Agents for the Treatment of Glioblastoma
(Elsevier Science BV, 2017) Cacciatore, Ivana; Fornasari, Erika; Marinelli, Lisa; Eusepi, Piera; Ciulla, Michele; Ozdemir, Ozlem; Di Stefano, Antonio
Glioblastoma is one of the most aggressive malignant primary brain cancer in adults. To date, surgery, radiotherapy and current pharmacological treatments are not sufficient to manage this pathology that has a high mortality rate (median survival 12-15 months). Recently, anticancer multi-targeted compounds have attracted much attention with the aim to obtain new drugs able to hit different biological targets that are involved in the onset and progression of the disease. Here, we report the synthesis of novel memantine-derived drugs (MP1-10) and their potential antitumor activities in human U87MG glioblastoma cell line. MP1-10 were synthetized joining memantine, which is a NMDA antagonist, to different histone deacetylase inhibitors to obtain one molecule with improved therapeutic efficacy. Biological results indicated that MP1 and MP2 possessed more potent anti-proliferative effects on U87MG cells than MP3-10 in a dose-dependent manner. MP1 and MP2 induced significant cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining. Both drugs also exhibited non-genotoxic and only mild cytotoxic effects in human whole blood cells. However, only MP1, showing good chemico-physical properties (solubility, LogP) and enzymatic stabilities in gastric and intestinal fluids, can be considered a suitable candidate for in vivo pharmacokinetic studies.
Molecular Genetics and Cytotoxic Responses to Titanium Diboride and Zinc Borate Nanoparticles on Cultured Human Primary Alveolar Epithelial Cells
(MDPI, 2022) Turkez, Hasan; Arslan, Mehmet Enes; Tatar, Arzu; Ozdemir, Ozlem; Sonmez, Erdal; Cadirci, Kenan; Mardinoglu, Adil
Titanium diboride (TiB2) and zinc borate (Zn3BO6) have been utilized in wide spectrum industrial areas because of their favorable properties such as a high melting point, good wear resistance, high hardness and thermal conductivity. On the other hand, the biomedical potentials of TiB2 and Zn3BO6 are still unknown because there is no comprehensive analysis that uncovers their biocompatibility features. Thus, the toxicogenomic properties of TiB2 and Zn3BO6 nanoparticles (NPs) were investigated on human primary alveolar epithelial cell cultures (HPAEpiC) by using different cell viability assays and microarray analyses. Protein-Protein Interaction Networks Functional Enrichment Analysis (STRING) was used to associate differentially expressed gene probes. According to the results, up to 10 mg/L concentration of TiB2 and Zn3BO6 NPs application did not stimulate a cytotoxic effect on the HPAEpiC cell cultures. Microarray analysis revealed that TiB2 NPs exposure enhances cellular adhesion molecules, proteases and carrier protein expression. Furthermore, Zn3BO6 NPs caused differential gene expressions in the cell cycle, cell division and extracellular matrix regulators. Finally, STRING analyses put forth that inflammation, cell regeneration and tissue repair-related gene interactions were affected by TiB2 NPs application. Zn3BO6 NPs exposure significantly altered inflammation, lipid metabolism and infection response activator-related gene interactions. These investigations illustrated that TiB2 and Zn3BO6 NPs exposure may affect different aspects of cellular machineries such as immunogenic responses, tissue regeneration and cell survival. Thus, these types of cellular mechanisms should be taken into account before the use of the related NPs in further biomedical applications.
NFBTA: A Potent Cytotoxic Agent Against Glioblastoma
(MDPI, 2019) Turkez, Hasan; da Nobrega, Flavio Rogerio; Ozdemir, Ozlem; Maia Bezerra Filho, Carlos da Silva; de Almeida, Reinaldo Nobrega; Tejera, Eduardo; de Sousa, Damiao Pergentino
Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the Piper genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; (E)-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.
Piplartine Analogues and Cytotoxic Evaluation Against Glioblastoma
(MDPI, 2018) da Nobrega, Flavio Rogerio; Ozdemir, Ozlem; Nascimento Sousa, Sheila Cristina S.; Barboza, Joice Nascimento; Turkez, Hasan; de Sousa, Damiao Pergentino
Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl) acrylate and 3-(3,4,5-trimethoxyphenyl) acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl) acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.
Synthesis and Anticancer Activity of Novel Ureas and Sulfamides Incorporating 1-Aminotetralins
(Elsevier Science Inc, 2017) Ozgeris, Bunyamin; Akbaba, Yusuf; Ozdemir, Ozlem; Turkez, Hasan; Goksu, Suleyman
Background and Aims. In the present study, a series of ureas and sulfamides derived from 1-aminotetralins were synthesized. For this purpose, urea and sulfamide analogues were synthesized from the reactions of substituted 1-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride. The anticancer activity of newly synthesized compounds was tested against human U-87MG glioblastoma and PC-3 prostate cancer cell lines. Cytotoxicity was examined using MTT and LDH release assays. Results. The obtained data revealed that tested compounds showed a variable degree of cytotoxic activity against the tested cell lines. 3-(5-methoxy-1,2,3,4-tetrahydronaphthalenl-y1)-1,1-dimethylurea (9) and 3-(6-methoxy-1,2,3,4-tetrahydronaphthalen-l-y1)-1, 1-dimethylurea (10) proved to be the most active cytotoxic members in this study. Conclusions. These two compounds could be considered as possible anticancer agents. (C) 2017 IMSS. Published by Elsevier Inc.
Synthesis of the 3,5-Diphenyl and Cytogenetic and Oxidative Alterations After Exposure of Cultured Human Whole Blood Cells
(Taylor & Francis AS, 2017) Akbas, Esvet; Celikezen, Fatih Caglar; Turkez, Hasan; Ozdemir, Ozlem; Ruzgar, Adem; Ergan, Erdem; Sahin, Ertan
The 3,5-diphenyl-1H-pyrazole was obtained by condensation reaction of dibenzoylmethane and thiosemicarbazide in acetic acid under conventional heating and microwave irradiation method. The structure of the 3,5-diphenyl-1H-pyrazole confirmed by IR, H-1, and C-13 NMR and X-ray diffraction and the geometry optimization was carried out using density functional theory (DFT) methods at B3LYP/6-31G, 6-31G(d), 6-31G(d, p), 6-311G(d, p), 6-311G(2d, 2p), 6-31+G(d, p), 6-311++G(d, p) levels. In addition, cytotoxic and oxidative effects were investigated in cultured human peripheral blood cells.