Bioengineering / Biyomühendislik

Permanent URI for this collectionhttps://hdl.handle.net/11147/4529

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Author: search.filters.author.Yılmaz, SinemHas files: No

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  • Article
    Citation - WoS: 4
    A Src/Abl Kinase Inhibitor, Bosutinib, Downregulates and Inhibits Parp Enzyme and Sensitizes Cells To the DNA Damaging Agents
    (Türk Biyokimya Derneği, 2018) Kırmızıbayrak, Petek Ballar; Yılmaz, Sinem; Yılmaz, Sinem; Günal, Selin; Tepedelen, Burcu Erbaykent; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Background: Poly(ADP-ribosyl)ation (PARylation) catalyzed mainly by PARP1 is a highly regulated posttranslational modification associated with several pathways in cellular physiology and genotoxic deoxyribonucleic acid (DNA) damage response. PAR polymers and PARP enzyme function in DNA integrity maintenance and several PARP inhibitors have entered clinical phase studies for cancer therapies. Material and methods: The effect of bosutinib, a dual Src/Abl kinase inhibitor, on PARylation was fluorometrically measured. The cytotoxic and chemosensitizing effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of DNA repair proteins and PARP enzyme were examined by immunoblotting. Results: In this study, bosutinib is characterized as a novel PARP inhibitor. Bosutinib inhibited oxidative stress-induced cellular PARylation and nuclear foci formation by downregulating PARP1 levels. Bosutinib was found to be more cytotoxic on Capan1 cells with BRCA2 mutation. Furthermore by acting as a chemosensitizer, bosutinib enhanced the cytotoxicity of doxorubicin (DOXO) and etoposide (ETP) by decreasing phosphorylation of DNA repair enzymes checkpoint kinase 1 (Chk1) and ataxia-telangiectasia mutated (ATM). Conclusion: By inhibition of both PARP and DNA damage checkpoint kinases, bosutinib increased the phospho-H2AX levels, an early indicator of DNA double strand breaks.
  • Conference Object
    Bioassay Guided Isolation of Naphthoquinones From Onosma Aksoyii, Investigation of Their Cytotoxic Properties
    (Georg Thieme Verlag, 2019) Kul, Demet; Bedir, Erdal; Karakoyun, Çiğdem; Yılmaz, Sinem; Yılmaz, Sinem; Pirhan, Ademi Fahri; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    The genus Onosma L. (Boraginaceae) includes about 230 species, distributed mainly in the Mediterranean region and Central Asia. Major constituents of Onosma species are alkaloids, naphthoquinones, polyphenols, phytosterols, terpenoids and fatty acids [1], [2]. Naphthoquinones are naturally widespread secondary metabolites deriving from some higher plants, fungi and bacteria. They exhibit significant biological activities such as cytotoxicity, antimalarial, antibacterial, antifungal and wound healing [2], [3]. Recently naphthoquinone derivatives have also been recognized as potent topoisomerase inhibitors [4].
  • Conference Object
    Citation - WoS: 1
    Telomerase Activators Derived From Astragalus Sapogenins Via Biotransformation With the Recently Discovered Endophytic Fungus Camarosporium Laburnicola
    (Georg Thieme Verlag, 2019) Küçüksolak, Melis; Yılmaz, Sinem; Ekiz, Güner; Duman, Seda; Duman, Seda; Bedir, Erdal; Yılmaz, Sinem; Küçüksolak, Melis; Ballar Kırmızıbayrak, Petek; Bedir, Erdal; 03.01. Department of Bioengineering; 01.01. Units Affiliated to the Rectorate; 01. Izmir Institute of Technology; 03. Faculty of Engineering
    Telomeres are nucleotide sequences that are located at the end of chromosomes shortening with each cell division. Telomerase is a reverse transcriptase enzyme, and it helps to replenish telomere ends that are truncated by aging and stress factors.