Browsing by Subject "Bioactivity"

Now showing 1 - 5 of 5

Open Access
Cytotoxic and bioactive properties of different color tulip flowers and degradation kinetic of tulip flower anthocyanins
(Pergamon Press, 2013) Sagdic, O.; Ekici, L.; Ozturk, I.; Tekinay, T.; Polat, B.; Tastemur, B.; Bayram, O.; Senturk, B.
This study was conducted to determine the potential use of anthocyanin-based extracts (ABEs) of wasted tulip flowers as food/drug colorants. For this aim, wasted tulip flowers were samples and analyzed for their bioactive properties and cytotoxicity. Total phenolic contents of the extracts of the claret red (126.55. mg of gallic acid equivalent (GAE)/g dry extract) and orange-red (113.76. mg GAE/g dry extract) flowers were the higher than those of the other tulip flowers. Total anthocyanin levels of the violet, orange-red, claret red and pink tulip flower extracts were determined as 265.04, 236.49, 839.08 and 404.45. mg pelargonidin 3-glucoside/kg dry extract, respectively and these levels were higher than those of the other flowers. The extracts were more effective for the inhibition of Listeria monocytogenes, Staphylococcus aureus and Yersinia enterocolitica compared to other tested bacteria. Additionally, the cytotoxic effects of five different tulip flower extracts on human breast adenocarcinoma (MCF-7) cell line were investigated. The results showed that the orange red, pink and violet extracts had no cytotoxic activity against MCF-7 cell lines while yellow and claret red extracts appeared to be toxic for the cells. Overall, the extracts of tulip flowers with different colors possess remarkable bioactive and cytotoxic properties. © 2013 Elsevier Ltd.
Open Access
Effects of PI3K/AKT/MTOR and VEGFR pathway inhibitors on liver cancer stem cells and bioactivities of novel pyrazolic chalcone derivatives on liver cancer
(2017-12) Kahraman, Deniz Cansen
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality, such that it the second most frequent cause of cancer death worldwide. Due to its heterogeneous composition and aggressive behavior, it is resistant to conventional therapies and also Sorafenib and Regorafenib which are FDA-approved multikinase inhibitors targeting pathways involved in angiogenesis and proliferation. The mechanisms behind the acquired resistance to Sorafenib were described as activation of compensatory pathways such as PI3K/Akt/mTOR, JAK-STAT, epithelial to mesenchymal transition (EMT), microenvironment and presence of cancer stem cells. Liver cancer stem cells originate from damaged and transformed hepatic progenitor cells (HPCs) which are found responsible for chemo-resistance, tumor relapse, and metastasis. For this reason, the effects of PI3K/Akt/mTOR inhibitors, Sorafenib and DNA intercalators on the enrichment of LCSCs were investigated. CD133+/EpCAM+ population from HCC cells were analyzed by flow cytometry after treatment with inhibitors, and effective inhibitors against LCSCs were further tested for their potential combinatorial effects together with Sorafenib. It was shown that upon treatment with Sorafenib or DNA intercalators the LCSCs were enriched, whereas Rapamycin (mTOR inhibitor), LY294002 (PI3K inhibitor) were able to inhibit the enrichment of LCSCs and reduced the CD133+/EpCAM+ population ratio. Combination studies revealed that when cells are treated initially with Rapamycin and then with Sorafenib, both the LCSC ratio and the sphere formation capacity of cells were reduced compared to cells treated with Sorafenib alone. To understand the alterations in gene expression induced by the inhibitors, a large panel of genes involved in regulation of cancer pathways were analyzed using Nanostring nCounter Technology. Systematic pathway analysis using Cytoscape Score Flow algorithm application allowed us to identify differential response genes involved in stemness. It was shown that genes involved in regulation of stem cells (Wnt and Notch pathway) were downregulated upon treatment with Rapamycin and DAPT (Notch pathway inhibitor), yet Sorafenib treatment resulted in differential regulation of these pathways, where JAG1 gene was found to be up-regulated. Interestingly, IL-8 expression was upregulated dramatically upon treatment with Sorafenib, but downregulated upon DAPT or Rapamycin treatment. Inhibition of IL-8 signaling resulted in reduction in both LCSC ratio and sphere formation capacity of HCC cells, which could be indicating the role of IL-8 signaling in the conservation of stemness features of LCSCs. For this reason, blockade of IL-8 signaling was suggested to be a promising therapeutic approach for HCC. Another topic in this thesis focuses on the potential of VEGFR2 TKIs and quinoids to inhibit both liver cancer cells and liver cancer stem cells. VEGFR TKIs such as Sorafenib, are widely studied for the treatment of many cancers, yet as mentioned above, there are many clinical studies providing the evidence that anti-VEGF or anti-VEGFR therapies lead to stable disease, which is then followed by disease progression in different cancer types. In recent years it has also been shown that antiangiogenic agents are increasing cancer stem cell population via generation of tumor hypoxia. Quinoids, on the other hand, are compounds that are selectively active in hypoxic conditions. Thus, the main aim of this study was to evaluate the bioactivities of compounds from each group on liver cancer cells and also to analyze their effects on the enrichment of LCSCs. Our results have shown that VEGFR2 TKIs were cytotoxic at lower concentrations compared to quinoids. However, it was shown that VEGFR2 TKIs are more likely to enrich LCSC population whereas some of the quinoids were able to reduce this ratio. With this information, a new concept called “aggressiveness factor”, which defines the potential of a compound to cause more aggressive cancer, was introduced. In the last part of this thesis, bioactivities of pyrazolic chalcone derivatives on HCC cell lines and their mechanism of action were investigated. Chalcones and pyrazolic structures are well known for their anti-cancer activities. Newly synthesized pyrazolic chalcone derivatives were tested against different cancer cells, and selection based on the IC50 values of compounds was made to analyze their effect on a panel of HCC cells. Results have shown that, compounds 39, 42, 49 and 52 were the most effective derivatives which had anti-proliferative activities in less than 5 μM concentrations. Further investigation of cell cycle progression and cell death mechanisms have revealed that compounds 42 and 52 caused cell cycle arrest at the G2/M phase and induced apoptotic cell death. Also, levels of cell cycle proteins, p21, CDK1, and phospho-CyclinB1 were shown to decrease upon treatment with these compounds.
Open Access
Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development
(Elsevier B.V., 2017) Bayyurt, B.; Tincer, G.; Almacioglu, K.; Alpdundar, E.; Gursel, M.; Gursel, I.
Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine. ï¿½ 2017 Elsevier B.V.
Open Access
Nanomaterials for bone tissue regeneration and orthopedic implants
(John Wiley & Sons, 2016-03-11) Gülseren, Gülcihan; Ceylan, Hakan; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Güler, Ayşe B.
Hierarchical organization and specialized composition of bone extracellular matrix (ECM) control the cellular processes including proliferation, migration, and differentiation for continuous modulation and maintenance of structure. For bone tissue regeneration, peptideor polymer‐based biomaterials have offered a framework to design interactive molecules displaying bone composite properties to mimic living bone tissue. This chapter reviews the structure and properties of peptide‐ and polymer‐based soft grafts for bone tissue regeneration, with a summary of upcoming goals and challenges in the future of these versatile materials. It basically covers types and applications of soft bone grafts, directed bone regeneration from biocompatible and bioactive biomaterials, and nanocomposite scaffolds for bone tissue regeneration. Bone regeneration studies have been primarily focused on polymers and synthetic proteins. The chapter describes some of the significant contribcutions to the field of bone regeneration with self‐assembled peptide structures.
Open Access
Three-Dimensional Laminin Mimetic Peptide Nanofiber Gels for In Vitro Neural Differentiation
(Wiley-VCH Verlag, 2017) Gunay, Gokhan; Sever, Melike; Tekinay, Ayse B.; Güler, Mustafa O.
The extracellular matrix (ECM) provides biochemical signals and structural support for cells, and its functional imitation is a fundamental aspect of biomaterial design for regenerative medicine applications. The stimulation of neural differentiation by a laminin protein-derived epitope in two-dimensional (2D) and three-dimensional (3D) environments is investigated. The 3D gel system is found to be superior to its 2D counterpart for the induction of neural differentiation, even in the absence of a crucial biological inducer in nerve growth factor (NGF). In addition, cells cultured in 3D gels exhibits a spherical morphology that is consistent with their form under in vivo conditions. Overall, the present study underlines the impact of bioactivity, dimension, and NGF addition, as well as the cooperative effects thereof, on the neural differentiation of PC-12 cells. These results underline the significance of 3D culture systems in the development of scaffolds that closely replicate in vivo environments for the formation of cellular organoid models in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim