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  • Küçük Resim
    Öğe
    Cytotoxic effects of silver nanoparticles synthesized using Asphodelus aestivus Brot. aqueous extract
    (Marmara Univ, 2023) Tastan, Pelin; Fafal, Tugce; Tuezuen, Burcu Suemer; Ozmen Yelken, Besra; Kayabasi, Cagla; Yilmaz Susluer, Sunde; Gunduz, Cumhur
    The aim of the study is to examine the cytotoxic, apoptotic effects and gene expressions of Asphodelus aestivus water extract (ASP) and silver nanoparticles (AgNPS) on decided cancer lines. Breast cancer cell lines MCF-7 and MDA-231; melanoma cancer lines MEWO and CHL-1; fibroblast cancer lines WI-38 and HEL 299 were selected for biological activities. xCELLigence system was used for cytotoxicity. Annexin V-EG FP Apoptosis detection kit was used for apoptosis and gene expressions were assessed by real time online RT-PCR by using cancer cell lines Qiagen kits. AgNPS showed significant cytotoxicity in all cell lines. The most prominent apoptosis was determined in MCF-7 cell line for AgNPS. It has been observed that the most important progress in gene expression, the suppression capacity of MUC1-C, a breast cancer-associated oncoprotein, is greatly increased by nanoparticle formation. In addition, cells that were not affected at all in MDA-MB-231 breast cancer oncoprotein started to suppress with nanoparticles. In conclusion, it was determined that silver nanoparticles increased the effect especially in breast cancer cell lines and could be considered for use.
  • Küçük Resim
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    The effects of PKI-402 on breast tumor models' radiosensitivity via dual inhibition of PI3K/mTOR
    (Taylor & Francis Ltd, 2023) Gasimli, Roya; Kayabasi, Cagla; Yelken, Besra Ozmen; Asik, Aycan; Sogutlu, Fatma; Celebi, Caglar; Susluer, Sunde Yilmaz
    PurposePI3K/Akt/mTOR pathway activation causes relapse and resistance after radiotherapy in breast cancer (BC). We aimed to radiosensitize BC cell lines to irradiation (IR) by PKI-402, a dual PI3K/mTOR inhibitor.MethodsWe performed cytotoxicity, clonogenicity, hanging drop, apoptosis and double-strand break detection, and phosphorylation of 16 essential proteins involved in the PI3K/mTOR pathway.ResultsOur findings showed that PKI-402 has cytotoxic efficiency in all cell lines. Clonogenic assay results showed that PKI-402 plus IR inhibited the colony formation ability of MCF-7 and breast cancer stem cell lines. Results showed that PKI-402 plus IR causes more apoptotic cell death than IR alone in the MCF-7 cells but did not cause significant changes in the MDA-MB-231. & gamma;-H2AX levels were increased in MDA-MB-231 in PKI-402 plus IR groups, whereas we did not observe any apoptotic and & gamma;-H2AX induction in BCSCs and MCF-10A cells in all treatment groups. Some pivotal phosphorylated proteins of the PI3K/AKT pathway decreased, several proteins increased and others did not change.ConclusionIn conclusion, if the combined use of PKI-402 with radiation is supported by in vivo studies, it can contribute to the treatment options and the course of the disease.
  • Küçük Resim Yok
    Öğe
    Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells
    (Routledge Journals, Taylor & Francis Ltd, 2022) Kayabasi, Cagla; Yilmaz Susluer, Sunde; Balci Okcanoglu, Tugce; Ozmen Yelken, Besra; Mutlu, Zeynep; Goker Bagca, Bakiye; Caliskan Kurt, Cansu
    Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose similar to 5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G(0)/G(1), S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML.