Researcher: Adıgüzel, Zelal
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Adıgüzel, Zelal
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Publication Metadata only Copper(II) and oxidovanadium(IV) complexes of chromone schiff bases as potential anticancer agents(Springer, 2022) Nunes, Patrique; Yıldızhan, Yasemin; Marques, Fernanda; Pessoa, Joao Costa; Correia, Isabel; Adıgüzel, Zelal; Ayhan, Ceyda Açılan; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; 251865; 219658We report the synthesis, characterization and biological screening of new chromone Schiff bases derived from the condensation of three 6-substituted-3-formyl-chromones with pyridoxal (HL1-3) and its Cu(II) complexes [Cu(L1-3)Cl], 1-3. For the 6-methyl derivative, HL2, the (VO)-O-IV-complex [VO(L-2)Cl] (5), as well as ternary Cu and (VO)-O-IV complexes with 1,10-phenanthroline (phen), [Cu(L-2)(phen)Cl] (4) and [VO(L-2)(phen)Cl] (6), were also prepared and evaluated. Their stability in aqueous medium and radical scavenging activity toward DPPH are screened, with [Cu(L-2)(phen)Cl] (4) showing hydrolytic stability and [VO(L-2)(phen)Cl] (6) high radical scavenging activity. Spectroscopic studies establish bovine serum albumin (BSA), a model for HSA, as a potential reversible carrier of [Cu(L-2)(phen)Cl] in blood with K-BC approximate to 10(5) M-1. The cytotoxic activity of a group of compounds is evaluated against a panel of human cancer cell lines of different origin (ovary, cervix, brain and breast) and compared to normal cells. Our results indicate that Cu complexes are more cytotoxic than the ligands but not selective towards cancer cells. The most potent complexes (4 and 6) are further evaluated for their apoptotic potential, induction of reactive oxygen species (ROS) and genotoxicity. Both complexes efficiently triggered cell death through apoptosis as evaluated by DNA morphology and TUNEL assay, increased ROS formation as determined by DCFDA (2',7'-dichlorodihydrofluorescein diacetate) analysis, and induced genotoxic damage as visualized via COMET assay in all cancer cells under study. Therefore, 4 and 6 may be potential precursor anticancer molecules, yet they need to be targeted toward cancer cells. [GRAPHICS] .Publication Metadata only Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells(Springer, 2020) Kiyga, Ezgi; Sengelen, Aslihan; Onay Ucar, Evren; N/A; Adıgüzel, Zelal; Faculty Member; School of Medicine; 251865High expression of heat shock proteins (HSP) in breast cancer has been closely associated with tumor cell proliferation and thus a poor clinical outcome. Quercetin, a good Hsp inhibitor as a dietary flavonoid, possesses anticarcinogenic properties. Although there are many studies on the effects of quercetin on Hsp levels in human breast cancer cells, research on elucidation of its molecular mechanism continues. Herein, we aimed to investigate the effect of quercetin on Hsp levels and whether quercetin is a suitable therapeutic for two breast cancer cell lines (MCF-7 and MDA-MB-231) representing breast tumors which differed in hormone receptor, aggressiveness and treatment responses. To examine the response to high and low doses of quercetin, the cells were treated with three doses of quercetin (10, 25 and 100 mu M) determined by MTT. The effects of quercetin on Hsp levels, apoptosis and DNA damage were examined by western blot analysis, caspase activity assay, comet assay and microscopy in human breast cancer cells. Compared to MDA-MB231 cells, MCF-7 cells were more affected by quercetin treatments. Quercetin effectively suppressed the expression of Hsp27, Hsp70 and Hsp90. While quercetin did not induce DNA damage, it triggered apoptosis at high levels. Although an increase in NF-kappa B levels is observed in the cells exposed to quercetin, the net result is the anticancer effect in case of Hsp depletion and apoptosis induction. Taken together our findings suggested that quercetin can be an effective therapeutic agent for breast cancer therapy regardless of the presence or absence of hormone receptors.Publication Metadata only Fabrication of a patterned scaffold using soft lithography technique to be used in cell growth applications(Springernature) Sariogullari, Hidayet; Aroguz, Ayse Z.; N/A; Adıgüzel, Zelal; Faculty Member; School of Medicine; 251865In recent years, within tissue engineering, cell growth on patterned surfaces have gained significant attention. Growing cells in patterns is important to manufacture polymeric tissues that can be used within the medical field. For this reason, the main focus of this study was to prepare patterned scaffolds using Titanium (Ti) and polyvinyl chloride (PVC) covered on microscope lamellas and examine their liability for cell growth. A polydimethylsiloxane stamp was initially prepared which was then used to transfer a predefined pattern onto PVC- and Ti-covered surfaces. Cell growth experiments were performed on the prepared materials by seeding L929 mouse fibroblasts. The growth of cells seeded on the surface of the scaffolds were spectroscopically followed using Neutral Red uptake assay. The results showed cell proliferation on both patterned surfaces, however, it was higher on Ti-covered samples. In addition, three different alkanethiols were tested for cell adhesion on patterned surfaces. A higher number of cell proliferation was observed with undecanethiol, which has a shorter alkane group among them. The morphological properties of the samples before and after cell-seeding were analyzed via scanning electron microscope and optical microscopy. Significant amount of cell proliferation was observed on all of the prepared samples.Publication Metadata only Anticancer investigation of platinum and copper-based complexes containing quinoxaline ligands(Elsevier, 2022) El-Beshti, Hager Sadek; Yildizhan, Yasemin; Kayi, Hakan; Cetin, Yuksel; Gercek, Zuhal; Ozalp-Yaman, Seniz; Adıgüzel, Zelal; Güngör Topçu, Gamze; Faculy Member; N/A; School of Medicine; N/A; 251865; N/AThis research focuses on synthesis and anticancer activity of trans-[(dichloro)bisdipyridlquinoxalino] and [(dichloro)bisdithienylquinoxalino]copper(II)/platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin (HSA) of the complexes were assessed with UV titration, thermal decomposition, viscometric, and fluorometric measurements. The nature of the binding of the complexes on DNA were revealed as electrostatic interaction between the cationic metal complexes ion and the negative phosphate groups of CT-DNA upon removal of the counter ion, chloride. In addition, our complexes induced a surface contact through the hydrophobic region of protein. Antitumor activity of the complexes against human glioblastoma A172, LN229, and U87 cell lines and human lung A549, human breast MDA-231, human cervix HeLa, and human prostate PC-3 cell lines were investigated by examining cell viability, oxidative stress, apoptosis, and migration/invasion. Cytotoxicity of the complexes was evaluated by MTT test. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of dipyridlquinoxalino and dithienylquinoxalino copper(II)/platinum(II) complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that trans-[(dichloro)bisdithenylquinoxalino]copper (II) (Cu(dtq)) has the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. Wound healing and invasion analysis results also supported the anticancer activity of Cu(dtq).Publication Open Access Temozolomide increases heat shock proteins in extracellular vesicles released from glioblastoma cells(Springer, 2022) Kıyga, E.; Önay Uçar, E.; Adıgüzel, Zelal; Faculty Member; School of MedicineBackground: Glioblastoma (GBM) is the most malignant and the fastest-progressing type of primary brain tumours. Temozolomide (TMZ) is a chemotherapeutic drug for the treatment of GBM. Extracellular vesicles (EVs) have been recently confirmed to have a substantial role in the GBM, and their contents released from GBM cells have been considered a target for treatment. The purpose of this study is to evaluate the impact of TMZ on heat shock proteins (HSPs) derived from EVs originated from GBM cell lines (U87-MG and LN229) and the significance of EVs in response to chemotherapy in GBM. Methods and results: NTA, ELISA, and immunoblotting were used to characterization studies of EVs and results showed that U87-MG cells released many EVs compared to LN229 cells. The effect of TMZ treatments on HSPs expression levels were assessed with immunoblotting and was found to be led to increases in HSF-1, Hsp90, Hsp70, Hsp60 and Hsp27 expression in GBM cells and their EV contents, which these increases are related to therapeutic resistance. What is more, in Real-time PCR studies showing which signalling pathways might be associated with these increases, it was observed that TMZ triggered the expression of RAD51 and MDM2 genes in cells and EV contents. More strikingly, we discover a correlation between EV and parental cells in regard of mRNA and protein level in both cell lines as a result of TMZ treatment. Conclusions: our data suggest of EVs in the treatment of GBM may have potential biomarkers that can be used to investigate the treatment response.