Person: ÇELİKLER KASIMOĞULLARI, SERAP
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ÇELİKLER KASIMOĞULLARI
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SERAP
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Publication Palladium (II) complex enhances ROS-dependent apoptotic effects via autophagy inhibition and disruption of multiple signaling pathways in colorectal cancer cells(Bentham Science Publ Ltd, 2021-01-01) Aydınlık, Şeyma; Erkısa, Merve; Arı, Ferda; Çelikler, Serap; Ulukaya, Engin; Aydınlık, Şeyma; ARI, FERDA; ÇELİKLER KASIMOĞULLARI, SERAP; 0000-0001-5238-2432; 0000-0002-6729-7908; 0000-0002-4177-3478; ABI-2909-2020; AAG-7012-2021; JCD-5015-2023Background: Inhibition of autophagy is reported to be a therapeutically effective strategy in overcoming resistance that is a deadly outcome in cancer. One of the most common reasons for chemo-resistance to treatment is the patients with tumors exhibiting a KRAS mutation, which occurs in approximately 40% of colorectal cancer patients.Objective: Hence, we assessed whether a Palladium (Pd)(II) complex is a promising anticancer complex, compared to 5-fluorouracil in KRAS wt HT-29 and KRAS mutant HCT-15 cells.Methods: HCT-15 and HT-29 cells were used for colorectal cancer and Chloroquine (CQ) was used as an inhibitor of autophagy. In this context, cells were treated with Pd(II) complex and 5-FU in combination with CQ for 48h and cell viability was measured by SRB assay. Cell death mode was examined with M30 and M65 ELISA assays, using annexin V/propidium iodide. Autophagy was determined by Acridine Orange (AO) staining. Furthermore, the expressions of various autophagy and apoptosis-related proteins were evaluated with Western blotting. Luminex assay and the level of Reactive Oxygen Species (ROS) were examined.Results: Cell viability was found to decrease in a dose-dependent manner and CQ enhanced cytotoxic effect in Pd(II) and 5-FU treated cells in colorectal cancer cells. Our data showed that inhibition of autophagic flux significantly increased intrinsic apoptosis through the activation of ROS. We showed that combinatorial treatment with CQ induced apoptosis via the caspase-dependent mitochondrial pathway. Luminex analysis revealed that the combination resulted in a down-regulation of NF-?B/AKT/CREB signaling pathways in both cell lines, however, decreased Erk1/2 protein expression was only observed after treatment with CQ combination in HCT-15 cells.Conclusion: We suggest that the inhibition of autophagy along with Pd(II) and 5-FU treatment has a synergistic effect on KRAS-mutant colorectal cancer cells. Autophagy inhibition by CQ promotes apoptosis via blockade of the NF-?B/AKT/CREB and activation of ROS.Publication Toxicity assessment of hypericum olympicum subsp. olympicum l. on human lymphocytes and breast cancer cell lines(Univ South Bohemia, 2020-01-01) Balıkçı, Necmiye; Sarımahmut, Mehmet; Arı, Ferda; Aztopal, Nazlıhan; Özel, Mustafa Zafer; Ulukaya, Engin; Çelikler, Serap; Balıkçı, Necmiye; SARIMAHMUT, MEHMET; ARI, FERDA; Aztopal, Nazlıhan; Ulukaya, Engin; ÇELİKLER KASIMOĞULLARI, SERAP; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0003-2647-5875; 0000-0002-6729-7908; 0000-0003-3118-8061; 0000-0003-4875-5472; 0000-0002-4177-3478; JCN-7113-2023; AAG-7012-2021; AAV-4886-2020; K-5792-2018; L-6687-2018; JCD-5015-2023; ENX-2092-2022There is a limited number of studies about the constituents of Hypericum olympicum subsp. olympicum and its genotoxic and cytotoxic potency. We examined the possible antigenotoxic/genotoxic properties of methanolic extract of H. olympicum subsp. olympicum (HOE) on human lymphocytes by employing sister chromatid exchange, micronucleus and comet assay and analyzed its chemical composition by GCxGC-TOF/MS. The anti-growth activity against MCF-7 and MDA-MB-231 cell lines was assessed by using the ATP viability assay. Cell death mode was investigated with fluorescence staining and ELISA assays. The major components of the flower and trunk were determined as eicosane, heptacosane, 2-propen-1-ol, hexahydrofarnesyl acetone and alpha-muurolene. HOE caused significant DNA damage at selected doses (250-750 mu g/ml) while chromosomal damage was observed at higher concentrations (500 and 750 mu g/ml). HOE demonstrated anti-growth activity in a dose-dependent manner between 3.13-100 mu g/ml. Pyknotic nuclei were observed at 100 mu g/ml concentration of HOE in both cell lines. In conclusion, HOE demonstrated cytotoxic effects in a cell type-dependent manner, however its genotoxic effects were observed at relatively higher doses.Publication Plants from northwestern anatolia display selective cytotoxicity and induce mitotic catastrophe: A study on anticancer and genotoxic activities(Wiley, 2023-08-16) Sarımahmut, Mehmet; Çelikler, Serap; SARIMAHMUT, MEHMET; ÇELİKLER KASIMOĞULLARI, SERAP; Fen Edebiyat Fakültesi; Biyoloji Bölümü; 0000-0003-2647-5875; 0000-0002-4177-3478; JCN-7113-2023; JCD-5015-2023Anatolia is rich in floristic diversity with a high rate of endemism. Eight plant species from northwestern Anatolia were evaluated for their anti-growth properties in two malignant (MCF-7 and MDA-MB-231) and a non-malignant (MCF-10A) breast cell lines. The two most active extracts, Achillea multifida (AME) and Astragalus sibthorpianus (ASE), induced apoptotic cell death in all cell lines. The major phenolic compounds in AME were identified as chlorogenic acid, and catechins in ASE. ASE displayed selective cytotoxicity against breast cancer cells, with DNA damage repair in non-malignant cells contributing to its selectivity. Conversely, AME induced DNA damage in a time-dependent manner and displayed a dual dose-dependent biological activity, resulting in mitotic catastrophe and apoptosis at different doses. Most plant species exhibited moderate to strong cytotoxicity, highlighting their medicinal and economic potential and the need for their protection.Publication Cytotoxic and genotoxic effects of an endemic plant of Turkey salvia kronenburgii on breast cancer cell lines(Wolters Kluwer Medknow Publications, 2019-07-01) Çebi, Ayşegül; Akgün, Egemen; Çelikler, Serap; Fırat, Mehmet; Özel, Mustafa Zafer; Ulukaya, Engin; Arı, Ferda; ÇELİKLER KASIMOĞULLARI, SERAP; ARI, FERDA; Uludağ Üniversite; Fen Bilimleri Fakültesi; Biyoloji Fakültesi; AAG-7012-2021; JCD-5015-2023Context: The natural products derived from plants are the important sources that can be used for breast cancer treatment. Salvia species and their derived products were recommended as potential antitumor substances.Aim: The potential cytotoxic and genotoxic effects of Salvia kronenburgii have been investigated on breast cancer cell lines, MCF-7 and MDA-MB-231.Materials and Methods: Determination of chemical compounds of S. kronenburgii was done using a gas chromatography coupled to time-of-flight mass spectrometry system and a dual-stage commercial thermal desorption injector. Growth inhibition of the S. kronenburgii was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and ATP viability assays. The cell death mode was detected by fluorescent dyes. Genotoxic effect of S. kronenburgii was measured by comet assay.Results: S. kronenburgii showed antiproliferative effect in a dose-dependent manner on MCF-7 and MDA-MB-231 cell lines by inducing apoptosis-like cell death. The pyknotic cell nuclei were observed at the cell lines in response to S. kronenburgii. Furthermore, significant increase was shown in genetic damage index and frequencies in the damaged cells.Conclusion: S. kronenburgii might be a promising natural source for cancer therapy. Further experiments need to be done in vivo to understand of the anticancer effects of this plant.Publication In vivo protective effect of Uridine, a pyrimidine nucleoside, on genotoxicity induced by Levodopa/Carbidopa in mice(Pergamon-Elsevier, 2015-08-01) Yaylagül, Esra Örenlili; Cansev, Mehmet; Kasımoğullari, Serap Çelikler; CANSEV, MEHMET; ÇELİKLER KASIMOĞULLARI, SERAP; Fen Edebiyat Fakültesi; Farmakoloji Ana Bilim Dalı; 0000-0003-2918-5064; M-9071-2019; JCP-8028-2023Parkinson's disease (PD) is a common neurodegenerative disorder that affects millions of people all over the world. Motor symptoms of PD are most commonly controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements. On the other hand, the effect of this treatment on bone marrow cells is unknown. Therefore, in this study, we aimed to investigate possible genotoxic effects of Levodopa and Carbidopa using male Balb/C mice. Our results showed that Levodopa alone or in combination with carbidopa caused genotoxicity in in vivo micronucleus test (mouse bone marrow) and Comet assay (blood cells). Furthermore, we showed that simultaneous administration of uridine, a pyrimidine nucleoside, reversed the genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by uridine treatment. These findings might enhance our understanding for the complications of a common Parkinson's treatment and confer benefit in terms of reducing a possible genotoxic effect of this treatment.Publication Simultaneous inhibition of PFKFB3 and GLS1 selectively kills KRAS transformed pancreatic cells(Academic Press, 2021-09-24) Özcan, Selahattin C.; Mutlu, Aydan; Altunok, Tuğba H.; Gürpınar, Yunus; Sarıoğlu, Aybike; Güler, Sabire; Muchut, Robertino J.; Iglesias, Alberto A.; Çelikler, Serap; Campbell, Paul M.; Yalçın, Abdullah; GÜLER, SABİRE; ÇELİKLER KASIMOĞULLARI, SERAP; YALÇIN, ABDULLAH; Mutlu, Aydan; Altunok, Tuğba H.; Sarıoğlu, Aybike; 0000-0003-1263-3799; 0000-0002-8287-6617; 0000-0002-4177-3478; 0000-0001-8519-8375; FNG-9051-2022; GCY-0775-2022; S-2474-2018; HTY-9355-2023; JCD-5015-2023; ABI-4164-2020Activating mutations of the oncogenic KRAS in pancreatic ductal adenocarcinoma (PDAC) are associated with an aberrant metabolic phenotype that may be therapeutically exploited. Increased glutamine utilization via glutaminase-1 (GLS1) is one such feature of the activated KRAS signaling that is essential to cell survival and proliferation; however, metabolic plasticity of PDAC cells allow them to adapt to GLS1 inhibition via various mechanisms including activation of glycolysis, suggesting a requirement for combinatorial anti-metabolic approaches to combat PDAC. We investigated whether targeting the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) in combination with GLS1 can selectively prevent the growth of KRAS-transformed cells. We show that KRAStransformation of pancreatic duct cells robustly sensitizes them to the dual targeting of GLS1 and PFKFB3. We also report that this sensitivity is preserved in the PDAC cell line PANC-1 which harbors an activating KRAS mutation. We then demonstrate that GLS1 inhibition reduced fructose-2,6-bisphosphate levels, the product of PFKFB3, whereas PFKFB3 inhibition increased glutamine consumption, and these effects were augmented by the co-inhibition of GLS1 and PFKFB3, suggesting a reciprocal regulation between PFKFB3 and GLS1. In conclusion, this study identifies a novel mutant KRAS-induced metabolic vulnerability that may be targeted via combinatorial inhibition of GLS1 and PFKFB3 to suppress PDAC cell growth. (c) 2021 Published by Elsevier Inc.