Browsing by Author "Taspinar, Filiz"

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The Antagonistic Effects of Temozolomide and Trichostatin a Combination on Mgmt and Dna Mismatch Repair Pathways in Glioblastoma
(Humana Press inc, 2023) Guven, Mustafa; Taspinar, Filiz; Denizler-Ebiri, Farika Nur; Castresana, Javier S.; Taspinar, Mehmet
Glioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373 MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RT-PCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment. It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines.
Exploring the Combined Anti-Cancer Effects of Sodium Butyrate and Celastrol in Glioblastoma Cell Lines: a Novel Therapeutic Approach
(Humana Press inc, 2024) Kartal, Bahar; Denizler Ebiri, Farika Nur; Gueven, Mustafa; Taspinar, Filiz; Canpinar, Hande; Cetin, Sedat; Taspinar, Mehmet
Glioblastoma, a highly aggressive and lethal brain cancer, lacks effective treatment options and has a poor prognosis. In our study, we explored the potential anti-cancer effects of sodium butyrate (SB) and celastrol (CEL) in two glioblastoma cell lines. SB, a histone deacetylase inhibitor, and CEL, derived from the tripterygium wilfordii plant, act as mTOR and proteasome inhibitors. Both can cross the blood-brain barrier, and they exhibit chemo- and radiosensitive properties in various cancer models. GB cell lines LN-405 and T98G were treated with SB and CEL. Cell viability was assessed by MTT assay and IC50 values were obtained. Gene expression of DNA repair, apoptosis, and autophagy-related genes was analyzed by RT-PCR. Cell cycle distribution was determined using flow cytometry. Viability assays using MTT assay revealed IC50 values of 26 mM and 22.7 mM for SB and 6.77 mu M, and 9.11 mu M for CEL in LN-405 and T98G cells, respectively. Furthermore, we examined the expression levels of DNA repair genes (MGMT, MLH-1, MSH-2, MSH-6), apoptosis genes (caspase-3, caspase-8, caspase-9), and an autophagy gene (ATG-6) using real-time polymerase chain reaction. Additionally, flow cytometry analysis revealed alterations in cell cycle distribution following treatment with SB, CEL and their combination. These findings indicate that SB and CEL may act through multiple mechanisms, including DNA repair inhibition, apoptosis induction, and autophagy modulation, to exert their anti-cancer effects in glioblastoma cells. This is the first study providing novel insights into the potential therapeutic effects of SB and CEL in glioblastoma.
Functional and Structural Neurodegenerative Activities of Ankaferd Bloodstopper in a Mouse Sciatic Nerve Model
(Spandidos Publ Ltd, 2024) Ustun, Ramazan; Oguz, Elif Kaval; Seker, Ayse; Taspinar, Filiz
Traumatic and postoperative hemorrhages are life-threatening complications. Ankaferd BloodStopper (ABS) is a potent topical hemostatic agent to stop bleeding. However, ABS is associated with nerve toxicity. The present study aimed to investigate the functional and structural neurodegenerative effects of ABS in a mouse model. A total of 30 male BALB/c mice, aged 6-8 weeks, were randomly divided into control group (no treatment), a sham group (treated with saline) and an experimental group (treated with ABS). In the saline and the ABS groups, the right sciatic nerve was surgically exposed and treated with saline or ABS, respectively. No surgical procedure was performed in the control group. On day 7 post-treatment, functional changes of the sciatic nerve were evaluated by a horizontal ladder rung walking task. Structural changes were assessed with immunohistochemistry. In the horizontal ladder rung walking test, the gait impairment was proportional to the severity of sciatic nerve damage, with the ABS group showing a significantly higher rate of errors than the control and saline groups. Immunohistochemistry demonstrated extensive degeneration and deformation in the axons and myelin sheath of the sciatic nerve in the ABS group. The results provide compelling evidence for the neurotoxicity of ABS.
Neuromuscular Degenerative Effects of Ankaferd Blood Stopper® in Mouse Sciatic Nerve Model
(Taylor & Francis Ltd, 2017) Ustun, Ramazan; Oguz, Elif Kaval; Delilbasi, Cagri; Seker, Ayse; Taspinar, Filiz; Oncu, Mehmet Resit; Oguz, Ahmet Regaip
Purpose: Ankaferd Blood Stopper((R)) (ABS), a licenced medicinal herbal extract, is commonly used as an effective topical haemostatic agent. This study is designed to investigate whether topical ABS application may cause peripheral nerve degeneration and neuromuscular dysfunction in a mouse sciatic nerve model.Methods: Twenty mice were randomly divided into two groups; an ABS treated experimental group and a saline-treated control group. Left sciatic nerves were treated with 0.3ml of ABS in the experimental group and 0.3ml of sterile saline in the control group for 5min. Peripheral nerve degeneration and neuromuscular dysfunction were evaluated by behavioural tests, electrophysiological analysis and weight ratio comparison of target muscles.Results: The motor function, assessed by the sciatic function index, was significantly impaired in ABS-treated animals as compared to the animals treated with saline. Motor coordination, evaluated with the rotarod test, was significantly decreased (-42%) in ABS-treated animals compared to the saline-treated animals. The degree of pain, assessed by the reaction latency to thermal stimuli (hot-plate test), was significantly prolonged (313%) in ABS-treated mice when compared to the saline-treated mice. ABS-treated mice showed a significant reduction in motor nerve conduction velocity (MNCV) (-52%) and the compound muscle action potential (CMAP) (-47%); however, it significantly prolonged onset latency (23%). The gastrocnemius muscles weight ratio of the ABS group was considerably lower than that of the control group.Conclusions: These findings demonstrate that ABS triggers peripheral nerve degeneration and functional impairment and, thus promotes a deterioration of sciatic nerves.
Synthesis of Novel Imidazopyridines and Their Biological Evaluation as Potent Anticancer Agents: a Promising Candidate for Glioblastoma
(Pergamon-elsevier Science Ltd, 2018) Guclu, Dilek; Kuzu, Burak; Tozlu, Israfil; Taspinar, Filiz; Canpinar, Hande; Taspinar, Mehmet; Menges, Nurettin
Novel imidazopyridine derivatives were synthesized according to a very simple protocol and then subjected to cytotoxicity testing against LN-405 cells. Two of the compounds exhibited antiproliferative effects on LN-405 cells at 10 and 75 mu M and were selected as lead compounds for further study. Safety experiment for lead compounds on WS1 was carried out and IC50 values were calculated as 480 and 844 mu M. LN-405 cell line were incubated with the lead compounds and then tested for DNA damage by comet assay and effects on cell cycle using flow cytometry. The results of these two tests showed that both lead compounds affected the G0/G1 phase and did not allow the cells to reach the synthesis phase. The log BB (blood-brain barrier) and Caco-2 permeability of the synthesized molecules were calculated and it was shown that imidazopyridine derivatives taken orally are likely to pass through gastrointestinal membrane and the blood-brain barrier.