Browsing by Author "Emsen, Bugrahan"

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The Anti-Cancer Efficacies of Diffractaic, Lobaric, and Usnic Acid: in Vitro Inhibition of Glioma
(Wolters Kluwer Medknow Publications, 2018) Emsen, Bugrahan; Aslan, Ali; Turkez, Hasan; Joughi, Ali Taghizadehghaleh; Kaya, Abdullah
Aims: Glioblastoma multiforme (GBM) shows the most aggressive invasion among primary brain tumors. In spite of the standard therapy methods such as surgery, radiotherapy, and chemotherapy, the mortalities are high in GBM patients owing to side effects. Some lichen secondary metabolites that have many bioactive functions exhibited anti-cancer efficacy toward many cancer types. The present study was undertaken to investigate proliferation change, oxidative status and DNA damage potentials of human U87MG-GBM, and primary rat cerebral cortex (PRCC) cells exposed to three lichen secondary metabolites. Materials and Methods: Different concentrations of lichen secondary metabolites including diffractaic acid (DA), lobaric acid (LA), and (+)-usnic acid (UA) were used for the treatments. PRCC cells were obtained from Sprague Dawley (R) rats. U87MG cell line was preferred as GBM cells. Results: The results showed that lactate dehydrogenase and 8-hydroxy-2'-deoxyguanosine levels increased in PRCC and U87MG cells in a clear dose-dependent manner. Inhibitory concentration 50% (IC50) values of LA, DA, and UA were calculated as 9.08, 122.26, 132.69 mg/L for PRCC cells and 5.77, 35.67, 41.55 mg/L for U87MG cells, respectively. Concentration of 10 mg/L of DA and UA demonstrated high anti-oxidant capacity on healthy PRCC cells. Conclusions: Overall, obtained data indicated that LA was highly toxic on GBM and PRCC cells. However, DA and then UA had high anti-oxidant capacity on PRCC cells. These results suggest that further studies that will be held on LA may play a critical role in GBM treatment.
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.
Boron Compounds Exhibit Protective Effects Against Aluminum-Induced Neurotoxicity and Genotoxicity: in Vitro and in Vivo Study
(MDPI, 2022) Turkez, Hasan; Yildirim, Serkan; Sahin, Elvan; Arslan, Mehmet Enes; Emsen, Bugrahan; Tozlu, Ozlem Ozdemir; Mardinoglu, Adil
Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds' genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.
Effects of Two Lichen Acids Isolated from Pseudevernia Furfuracea (L.) Zopf in Cultured Human Lymphocytes
(Walter de Gruyter GmbH, 2018) Emsen, Bugrahan; Togar, Basak; Turkez, Hasan; Aslan, Ali
The present study aims at assessing the efficacies of olivetoric acid (OA) and physodic acid (PA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) in human lymphocytes (HLs) in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to establish cytotoxicity in HLs. Besides, oxidative stress and genotoxicity were monitored by estimating the changes of total oxidative stress (TOS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, respectively, in HLs. At the same time, OA- and PA-induced total antioxidant capacity (TAC) levels in HLs were determined. Although especially low concentrations of OA (IC50 = 109.94 mg/L) and PA (IC50 = 665.49 mg/L) did not show cytotoxic effect at high levels in HLs, it was revealed that cytotoxicity was significantly (p 0.05) increase in the presence of all treatments (0.5-100 mg/L) of PA, TAC level was increased by PA applications in certain concentrations (0.5-10 mg/L). Overall, the obtained data indicate that OA and especially PA as lichen compounds that do not cause oxidative stress can be a new resource of therapeutics as recognized in the present study with their high antioxidant features.
Glioblastoma Multiformede Friedelinin Antikanser Aktivitesinin in Vitro İncelenmesi
(2018) Emsen, Bugrahan; Engin, Tubanur; Turkez, Hasan
Pek çok kanser hastalığında destek için kullanılan farklı bitkisel yöntemler vardır. Likenler benzersiz bitkisel bileşikler içeren önemli organizmalardır ve farklı antikanser aktivitelerine sahip oldukları bilinmektedir. Bu özelliklerden yola çıkarak, mevcut çalışma, beyin kanseri türleri içerisinde tehlikeli habis özellikler gösteren glioblastoma multiformeye (GBM) karşı bir liken bileşiği olan friedelinin (FRI) antikanser aktivitesini araştırmayı amaçlamıştır. FRI'nın yan etki düzeyini belirlemek için insan U87MG- GBM kanser hücre hatları ve Sprague-Dawley sıçanlarından izole edilen primer sıçan serebral korteks (PSSK) kanserli olmayan hücreler kullanılmıştır. Denemelerde, FRI'nın farklı konsantrasyonlarının sitotoksik (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) ve laktat dehidrogenaz (LDH) testleri ile), antioksidan (toplam antioksidan kapasite (TAK) testi ile), pro-oksidan (toplam oksidatif stres (TOS) ile) ve genotoksik (8-hidroksi-2′-deoksiguanozin (8-OH-dG) testi ile) aktiviteleri test edilmiştir. Çalışma sonucunda MTT uygulaması, FRI'nın PSSK hücrelerine kıyasla U87MG hücreleri üzerinde daha yüksek sitotoksik aktivite gösterdiğini ortaya koymuştur (sırasıyla medyan inhibitör konsantrasyonu (IC 50 ): 1271.77 ve 46.38 mg/L). U87MG hücreleri temel alındığında, LDH ve TOS aktiviteleri arasında anlamlı bir pozitif korelasyon olduğu saptanmıştır. Sağlıklı PSSK hücrelerinde, TAK ve hücre canlılığı arasındaki yüksek pozitif korelasyon FRI'nın antioksidan kapasitesini sergilemiştir. Sonuç olarak, mevcut çalışmadan elde edilen sonuçlar, GBM'ye karşı antikanser bileşiği kaynağı olarak antioksidan kapasiteye sahip doğal ürün potansiyelini ortaya koymuştur.
In Vitro Antitumor Activities of the Lichen Compounds Olivetoric, Physodic and Psoromic Acid in Rat Neuron and Glioblastoma Cells
(Taylor & Francis Ltd, 2016) Emsen, Bugrahan; Aslan, Ali; Togar, Basak; Turkez, Hasan
Context Since methods utilised in the treatment of glioblastoma multiforme (GBM) are inadequate and have too many side effects, usage of herbal products in the treatment process comes into prominence. Lichens are symbiotic organisms used for medicinal purposes for many years. There are various anticancer treatments about components of two lichen species used in the present study.Objective Antitumor potential of three lichen secondary metabolites including olivetoric acid (OLA) and physodic acid (PHA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) and psoromic acid (PSA) isolated from Rhizoplaca melanophthalma (DC.) Leuckert (Lecanoraceae) were investigated on human U87MG-GBM cell lines and primary rat cerebral cortex (PRCC) cells for the first time.Materials and methods PRCC cells used as healthy brain cells were obtained from Sprague-Dawley rats. The treatments were carried out on the cells cultured for 48h. Cytotoxic effects of different concentrations (2.5, 5, 10, 20 and 40mg/L) of metabolites on the cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. Total antioxidant capacity (TAC) and total oxidant status (TOS) parameters were used for assessing oxidative alterations. Oxidative DNA damage potentials of metabolites were investigated via evaluating 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels.Results Median inhibitory concentration (IC50) values of OLA, PHA and PSA were 125.71, 698.19 and 79.40mg/L for PRCC cells and 17.55, 410.72 and 56.22mg/L for U87MG cells, respectively. It was revealed that cytotoxic effects of these metabolites showed positive correlation with concentration, LDH activity and oxidative DNA damage.Discussion and conclusion The present findings obtained in this study revealed that primarily OLA and then PSA had high potential for use in the treatment of GBM.
In Vitro Cytotoxic, Genotoxic, Embryotoxic and Oxidative Damage Potentials by Empagliflozin
(Pleiades Publishing Inc, 2024) Cadirci, Kenan; Turkez, Hasan; Tozlu, Ozlem Ozdemir; Yapca, Omer Erkan; Bayrak, Muharrem; Emsen, Bugrahan; Mardinoglu, Adil
Empagliflozin (EMPA) is a potent, competitive and selective sodium glucose cotransporter-2 (SGLT-2) inhibitor that ameliorates blood glucose with the insulin-independent manner. EMPA reduces weight and blood pressure of patients with type 2 diabetes mellitus (T2DM) without developing hypoglycemic risk. To the best of our knowledge, its safety profiling has not been evaluated on human blood cell cultures yet. Again, the embryotoxicity potential by EMPA is still unclear. Therefore, in this investigation we aimed to evaluate the in vitro cytotoxic, genotoxic and embryotoxic damage potential as well as antioxidative/oxidative effects by EMPA in cultured human blood and human pluripotent embryonal carcinoma NT2 cells for the first time. Cell cultures (n = 5) were exposed to different concentrations ranging from 3.25 to 100 mg/L of EMPA for 48 and 72 h. Cell viability was measured by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. The alterations in antioxidant/oxidant activity were monitored via measuring the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels. For evaluating the genotoxicity of EMPA chromosomal aberration (CA) assay was performed. The present results revealed that EMPA did not induce cytotoxic or genotoxic damage on healthy human blood cells. Moreover, EMPA exerted non-embryotoxic property and supported antioxidative capacity and decreased the oxidative stress in cultured human blood cells. Our results supported the safe and advantageous use of EMPA for the treatment of T2DM.
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.
Potential Anticancer Effect of Carvacrol Codrugs on Human Glioblastoma Cells
(Bentham Science Publishing Ltd, 2021) Yazici, Aysenur; Marinelli, Lisa; Cacciatore, Ivana; Emsen, Bugrahan; Eusepi, Piera; Di Biase, Giuseppe; Turkez, Hasan
Background: Essential oils are considered as promising sources of novel anticancer compounds. Carvacrol (CVC), the major constituent of many aromatic plants including oregano and thymus, is endowed with curative properties on different cancers, including liver, colon, and lung. Little information is available regarding the potential of CVC for the treatment of brain cancers, notably Glioblastoma Multiforme (GBM). Objective: In this work, we investigated the in vitro effect of CVC codrugs (CVC1-8), synthesized by direct-coupled co-drug strategies, on human glioblastoma cell line (U87-MG) for the first time. Methods: Cell viability was detected by MTT and LDH assays while expression levels of important genes ( such as EGFR, NFKB1A, AKT1, AKT2, and others) associated with GBM and inflammatory pathways were detected by PCR array. Results: Results showed that CVC1-8 codrugs induced cytotoxicity and positive alterations in molecular responses on U87MG cells. Particularly, important pathways (such as PI3K/PTEN/AKT) involved in the onset and progression of GBM resulted in modulation by CVC3 and CVC8. Conclusion: Our results suggest that CVC3 and CVC8 could be suitable candidates for further investigation to develop new strategies for the prevention and/or treatment of GBM.