Browsing by Subject "cytotoxicity"
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Item Open Access Chitosan polysaccharide suppress toll like receptor dependent immune response(Turkish Society of Immunology, 2015) Tincer G.; Bayyurt, B.; Arıca, Y.M.; Gürsel İ.Objectives: Chitosan is a widely used vaccine or anti-cancer delivery vehicle. In this study, we investigated the immunomodulatory effect of chitosan/pIC nanocomplexes on mouse immune cells. Materials and methods: Proliferative and cytotoxic features of chitosan were tested via CCK-8 assay on RAW 264. 7. IL-1β production was assessed via ELISA from PEC supernatants. TNF-α, and NO induction from chitosan treated RAW cells detected by ELISA and Griess assay, respectively. mRNA message levels of TLRs and cytokines on macrophages in response to chitosan/pIC nanocomplex treatments were evaluated by RT-PCR. Results: Results revealed that chitosan is non-toxic to cells, however, proliferative capacities of macrophages were reduced by chitosan administration. Mouse PECs treated with chitosan, led to NLRP3 dependent inflammasome activation as evidenced by dose-dependent IL-1β secretion. Chitosan/pIC nanocomplexes did not improve immunostimulatory action of pIC on RAW cells, since TNF-α and NO productions remained unaltered. Expression levels of several TLRs, CXCL-16 and IFN-α messages from mouse splenocytes were down regulated in response to chitosan/pIC nanocomplex treatment. Conclusion: Our results revealed that chitosan is an anti-proliferative and inflammasome triggering macromolecule on immune cells. Utilization of chitosan as a carrier system is of concern for immunotherapeutic applications. © 2015 Turkish Journal of Immunology.Item Open Access The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity(Nature Publishing Group, 2015) Sag, D.; Cekic, C.; Wu, R.; Linden J.; Hedrick, C.C.ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1-/- mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1-/- mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1-/- macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer. © 2015 Macmillan Publishers Limited. All rights reserved.Item Open Access Cytotoxic activities of some benzothiazole-piperazine derivatives(Taylor and Francis Ltd, 2015) Gurdal, E.E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Compound 1d is highly cytotoxic against all tested cancer cell lines. Further investigation of compound 1d by Hoechst Staining and Fluorescence-Activated Cell Sorting Analysis (FACS) revealed that this compound causes apoptosis by cell cycle arrest at subG1 phase. © 2014 Informa UK Ltd. All rights reserved.Item Open Access In vitro biocompatibility of plasma-aided surface-modified 316L stainless steel for intracoronary stents(Institute of Physics Publishing, 2010) Bayram, C.; Mizrak, A.K.; Aktürk, S.; Kurşaklioǧlu H.; Iyisoy, A.; Ifran, A.; Denkbaş, E.B.316L-type stainless steel is a raw material mostly used for manufacturing metallic coronary stents. The purpose of this study was to examine the chemical, wettability, cytotoxic and haemocompatibility properties of 316L stainless steel stents which were modified by plasma polymerization. Six different polymeric compounds, polyethylene glycol, 2-hydroxyethyl methacrylate, ethylenediamine, acrylic acid, hexamethyldisilane and hexamethyldisiloxane, were used in a radio frequency glow discharge plasma polymerization system. As a model antiproliferative drug, mitomycin-C was chosen for covalent coupling onto the stent surface. Modified SS 316L stents were characterized by water contact angle measurements (goniometer) and x-ray photoelectron spectroscopy. C1s binding energies showed a good correlation with the literature. Haemocompatibility tests of coated SS 316L stents showed significant latency (t-test, p < 0.05) with respect to SS 316L and control groups in each test. © 2010 IOP Publishing Ltd.Item Open Access Synthesis and anticancer activity evaluation of some benzothiazole-piperazine derivatives(Bentham Science Publishers B.V., 2015) Gurdal, E.E.; Buclulgan, E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compounds cause apoptosis by cell cycle arrest at subG1 phase. © 2015 Bentham Science Publishers.Item Open Access Synthesis of 3-aroyl-4-aryl-1-isopropylamino-4-piperidinols and evaluation of the cytotoxicities of the compounds against human hepatoma and breast cancer cell lines(Taylor and Francis Ltd, 2015) Kucukoglu, K.; Mete, E.; Cetin-Atalay, R.; Gul H.I.Some 4-piperidinol derivatives were synthesized and their cytotoxicity was tested against human hepatoma (Huh7) and breast cancer (T47D) cells. Aryl part was changed as phenyl in 2a, 4-methylphenyl in 2b, 4-methoxyphenyl in 2c, 4-chlorophenyl in 2d, 4-fluorophenyl in 2e, 4-bromophenyl in 2f, 4-nitrophenyl in 2g and 2-thienyl in 3. Compounds were synthesized and reported for the first time by this study except 2a and 2d. Chemical structures were confirmed by 1H NMR, 13C NMR, IR, MS and elemental analyses. Compounds 2a (3.1 times), 2c (3.8 times), 2f (4.6 times), 2g (1.3 times) and 3 (3.2 times) had 1.3-4.6 times higher cytotoxic potency than the reference compound 5-FU against Huh7 cell line while all the compounds synthesized had shown lower activities against T47D cell line than 5-FU. In the light of these results, compounds 2a, 2c, 2f, 2g and 3 may serve as model compounds for further studies. © 2014 Informa UK Ltd.Item Open Access Ynamide Click chemistry in development of triazole VEGFR2 TK modulators(Elsevier Masson SAS, 2015) Vojtičková, M.; Dobiaš J.; Hanquet G.; Addová G.; Cetin-Atalay, R.; Yildirim, D.C.; Boháč, A.Structure novelty, chemical stability and synthetic feasibility attracted us to design 1,2,3-triazole compounds as potential inhibitors of VEGFR2 tyrosine kinase. Novel triazoles T1-T7 were proposed by oxazole (AAZ from PDB: 1Y6A)/1,2,3-triazole isosteric replacement, molecular modelling and docking. In order to enable synthesis of T1-T7 we developed a methodology for preparation of ynamide 22. Compound 22 was used for all Click chemistry reactions leading to triazoles T1-T3 and T6-T7. Among the obtained products, T1, T3 and T7 specifically bind VEGFR2 TK and modulate its activity by concentration dependent manner. Moreover predicted binding poses of T1-T7 in VEGFR2 TK were similar to the one known for the oxazole inhibitor AAZ (PDB: 1Y6A). Unfortunately the VEGFR2 inhibition by triazoles e.g. T3 and T7 is lower than that determined for their oxazole bioisosters T3-ox and AAZ, resp. Different electronic properties of 1,2,3-triazole/oxazole heterocyclic rings were proposed to be the main reason for the diminished affinity of T1-T3, T6 and T7 to an oxazole AAZ inhibitor binding site in VEGFR2 TK (PDB: 1Y6A or 1Y6B). Moreover T1-T3 and T6 were screened on cytotoxic activity against two human hepatocellular carcinoma cell lines. Selective cytotoxic activity of T2 against aggressive Mahlavu cells has been discovered indicating possible affinity of T2 to Mahlavu constitutionally active PI3K/Akt pathway. © 2015 Elsevier Masson SAS.