Browsing by Author "Cevatemre, Buse"
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Item Activity of pelargonium quercetorum agnew by inducing apoptosis-like cell death on non-small cell lung cancer cell lines(Wiley, 2014-11) Fırat, Mehmet; Yılmaz, Yusuf; Aztopal, Nazlıhan; Cevatemre, Buse; Ulukaya, Engin; Şimşek, Mehmet; Arı, Ferda; Egemen, Didem; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; K-5792-2018Item Addition of niclosamide to palladium(II) saccharinate complex of terpyridine results in enhanced cytotoxic activity inducing apoptosis on cancer stem cells of breast cancer(Pergamon-Elsevier, 2015-09-01) Karakaş, Didem; Cevatemre, Buse; Aztopal, Nazlıhan; Arı, Ferda; Yılmaz, Veysel Turan; Ulukaya, Engin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; 0000-0003-3118-8061; 0000-0002-2849-3332; 0000-0002-3781-6834; 0000-0002-6729-7908; L-6687-2018; K-5792-2018; AHD-2050-2022; L-7238-2018; L-6682-2018; AAG-7012-2021; AAV-4886-2020; 56422040600; 55693788600; 55853882900; 24376085300; 56441123900; 6602927353Wnt signaling is one of the core signaling pathways of cancer stem cells (CSCs). It is re-activated in CSCs and plays essential role in the survival, self-renewal and proliferation of these cells. Therefore, we aimed to evaluate the cytotoxic effects of palladium(II) complex which is formulated as [PdCl(terpy)](sac)2H(2)O and its combination with niclosamide which is an inhibitor of Wnt signaling pathway associated with breast cancer stem cells. Characteristic cell surface markers (CD44(+)/CD24(-)) were determined by flow cytometry in CSCs. ATP viability assay was used to determine the cytotoxic activity. The mode of cell death was evaluated morphologically using fluorescence microscopy and biochemically using M30 ELISA assay as well as performing qPCR. Our study demonstrated that the combination of niclosamide (1.5 mu M) and Pd(II) complex (12.5, 25 and 50 mu M) at 48 h has enhanced cytotoxic activity resulted from the induction of apoptosis (indicated by the presence of pyknotic nuclei, increments in M30 and over expression of proapoptotic genes of TNFRSF10A and FAS). Importantly, the addition of niclosamide resulted in the suppression of autophagy (proved by the decrease in ATG5 gene levels) that might have contributed to the enhanced cytotoxicity. In conclusion, the application of this combination may be regarded as a novel and effective approach for the treatment of breast cancer due to its promising cytotoxic effect on cancer stem cells that cause recurrence of the disease.Item Additive enhancement of apoptosis by TRAIL and fenretinide in metastatic breast cancer cells in vitro(Elsevier , 2014-03-13) Dimas, K.; Yerlikaya, Azmi; Ulukaya, Engin; Sarımahmut, Mehmet; Cevatemre, Buse; Arı, Ferda; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0003-2647-5875; 0000-0002-6729-7908; 0000-0003-4875-5472; K-5792-2018; AAG-8288-2021; AAG-7012-2021; AHD-2050-2022; 6602927353; 44661687400; 55693788600; 24376085300Item Anti-growth effect of a novel trans-dichloridobis[2-(2-hydroxyethyl)pyridine] platinum (II) complex via induction of apoptosis on breast cancer cell lines(Elsevier, 2015-08-01) Oral, Arzu Yilmaztepe; Cevatemre, Buse; Sarimahmut, Mehmet; Icsel, Ceyda; Yilmaz, Veysel Turan; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Kimya Bölümü.; 0000-0003-0463-6818; 0000-0002-0437-6385; 0000-0003-2647-5875; 0000-0002-2717-2430; 0000-0002-2849-3332; 0000-0003-4875-5472; A-5841-2017; AHD-2050-2022; AAG-8288-2021; AAI-3342-2021; L-7238-2018; K-5792-2018; 23091316500; 55693788600; 44661687400; 55551960400; 56441123900; 6602927353Breast cancer still continues to be the leading cause of cancer-related mortality in women worldwide. Although advances have been made in the treatment of this disease during the past decade, new approaches and novel compounds are urgently needed. The aim of this study was to evaluate the cytotoxic activity of trans-[PtCl2(2-hepy)(2)] [2-hepy=2-(2-hydroxyethyl) pyridine] on breast cancer cell lines, MCF-7 and MDA-MB-231. The platinum (II) complex was synthesized and characterized by our laboratory working group. Anti-growth effect was assayed by the MTT and ATP viability assays and also monitored real-time using xCELLigence system. The mode of cell death was evaluated by using the fluorescence microscopy (Hoechst 33342 + Calcein-AM + Propidium iodide staining), Western blotting (cleaved PARP and caspase 3, total caspase 8), flow cytometry (quantitative analysis of live, early/late apoptotic, dead cells and caspase 3/7 activity) and the RT-PCR (the genes analyzed were BCL-2L10, BIK, BAX, BCL-2, FASLG, HRK, TNFRSF10B, and TNFRSF10A). The platinum (II) complex had anti-growth effect in a dose dependent manner in vitro. Cells were killed by apoptosis as evidenced by the pyknotic nuclei, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the complex might represent a potentially active novel drug for the breast cancer treatment and warrants further studies due to its promising cytotoxic activity.Item Apoptosis-inducing effect of a palladium(II) saccharinate complex of terpyridine on human breast cancer cells in vitro and in vivo(Pergamon-Elsevier Science, 2014-09-01) İkitimur, Elif Armutak; Arı, Ferda; Cevatemre, Buse; Aztopal, Nazlıhan; Yılmaz, Veysel Turan; Ulukaya, Engin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; 0000-0003-3118-8061; 0000-0002-2849-3332; 0000-0002-6729-7908; 0000-0002-7359-6568; L-6687-2018; K-5792-2018; L-7238-2018; AAG-7012-2021; D-2901-2019; 24376085300; 55693788600; 55853882900; 7006269202; 6602927353The anti-growth effect of a palladium(II) complex-[PdCl(terpy)](sac)center dot 2H(2)O] (sac = saccharinate, and terpy = 2,2':6',2 ''-terpyridine)-was tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. Anti-growth effect was assayed by the MTT and ATP viability assays in vitro and then confirmed on Balb/c mice in vivo. The mode of cell death was determined by both histological and biochemical methods. The Pd(II) complex had anti-growth effect on a dose dependent manner in vitro and in vivo. The cells died by apoptosis as evidenced by the pyknotic nucleus, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the palladium(II) saccharinate complex of terpyridine represents a potentially active novel complex for the breast cancer treatment, thus warrants further studies.Item Breast cancer stem cells are more resistant than parental cells to a novel palladium (II) saccharinate complex(Elsevier, 2014-07) Karakaş, Didem; Aztopal, Nazlıhan; Cevatemre, Buse; Arı, Ferda; Oral, Arzu Yılmaztepe; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0003-3118-8061; 0000-0002-6729-7908; 0000-0002-2849-3332; 0000-0002-3781-6834; 0000-0003-0463-6818; L-6687-2018; AAG-7012-2021; L-7238-2018; L-6682-2018; A-5841-2017; K-5792-2018Item Cancer stem cells: emerging actors in both basic and clinical cancer research(Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, 2014-09-09) Karakaş, Didem; Cevatemre, Buse; Ulukaya, Engin; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; 0000-0002-3781-6834; 0000-0003-4875-5472; L-6682-2018; AHD-2050-2022; K-5792-2018; 56422040600; 55693788600; 6602927353Cancer stem cells (CSCs) are a small subset of cancer cells within a tumor that are responsible for tumorigenesis and contribute to drug resistance. The CSC displays an anchorage-independent survival, active DNA-repair capacity, and relative quiescence and is capable of self-renewing and maintaining tumor growth and heterogeneity. At the molecular level, there are several signaling pathways (e. g., Wnt/beta-catenin, Notch, and Hedgehog) to control CSC properties and alteration of these pathways has been recognized as an essential step for CSC transformation. Emerging evidence suggests that CSCs are clinically relevant. These cells are resistant to conventional chemotherapy and radiation treatment. Therefore, CSCs are thought to be the most important targets for anticancer therapy. In this review, we describe the characteristics of CSCs and how to isolate them based on some of their properties, as well as their importance in oncology.Item Combination of esomeprazole with chemotherapeutics results in more pronounced cytotoxic effect via apoptosis on A549 nonsmall-cell lung cancer cell line(TÜBİTAK, 2016-09-22) Yılmaztepe, Oral Arzu; Oral, Haluk Barbaros; Sarımahmut, Mehmet; Cevatemre, Buse; Özkaya, Güven; Korkmaz, Şeniz; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; 0000-0003-0463-6818; 0000-0003-2647-5875; 0000-0003-0297-846X; K-7285-2012; AAG-8288-2021; A-4421-2016; K-5792-2018; 26425326300; 7004498001; 44661687400; 55693788600; 16316866500; 36666461900; 6602927353The vacuolar (H+)-ATPases that pump H+ from the cytoplasm to extracellular compartments can alter the pH of the tumor microenvironment. Esomeprazole can effectively inhibit vacuolar (H+)-ATPases and may increase the effectiveness of chemotherapeutics. Therefore, we used esomeprazole in combination with cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine on the A549 nonsmall-cell lung cancer cell line. Cisplatin and carboplatin combinations with esomeprazole exhibited superior cytotoxicity compared to the other selected chemotherapeutics. Low-dose combinations of esomeprazole with either cisplatin or carboplatin resulted in synergistic interaction. We examined cytotoxic activity of these combinations with the xCELLigence real-time cytotoxicity assay and detected that esomeprazole combinations with both 100% test drug concentrations of cisplatin and carboplatin shifted the antiproliferative effects of these agents towards a cytotoxic effect in a dose-dependent manner. Cell death mode was investigated by M30 assay, Annexin-V-FITC fluorescence imaging, and determination of PARP cleavage in western blotting. The cells treated with the cisplatin and esomeprazole combination displayed characteristic features of apoptosis such as elevated M30 levels, Annexin-V staining, and PARP cleavage. In conclusion, these novel combinations resulted in higher sensitivity of tumors to chemotherapeutics, thereby warranting further in vivo experiments for proof of the concept.Item Combination of fenretinide and indole-3-carbinol results in synergistic cytotoxic activity inducing apoptosis against human breast cancer cells in vitro(Lippincott Williams & Wilkins, 2013-07) Kaçar, Ömer; Adıgüzel, Zelal; Açılan, Ceyda; Cevatemre, Buse; Arı, Ferda; Sarımahmut, Mehmet; Oral, Arzu Yılmaztepe; Dere, Egemen; Ulukaya, Engin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; 0000-0002-6729-7908; 0000-0003-0463-6818; AAG-7012-2021; AHD-2050-2022; AAH-5068-2021; K-5792-2018; A-5841-2017; 55693788600; 2437608530; 44661687400; 23091316500; 6603627015; 6602927353The outcome in patients with breast cancer is not satisfactory to date, although new chemotherapy regimens have been introduced in clinics. Therefore, novel approaches are required for better management of patients with breast cancer. In this study, we tested the cytotoxic activity of a new combination of fenretinide, a synthetic retinoid, with indole-3-carbinol, a natural product present in vegetables such as broccoli and cabbage, against MCF-7 (estrogen receptor-positive) and MDA-MB-231 (estrogen receptor-negative) cell lines. It has been found that the combination resulted in more powerful cytotoxic activity, by induction of apoptosis, compared with that when they were used singly. In conclusion, this novel combination warrants in-vivo experiments to elucidate its possible use in the treatment of breast cancer.Item Cytotoxic and apoptotic effects of the combination of palladium (II) 5,5-diethylbarbiturate complex with bis(2-pyridylmethyl)amine and curcumin on non small lung cancer cell lines(Elsevier, 2017-01-25) Ulukaya, Engin; Tunç, Duygu; Dere, Egemen; Karakaş, Didem; Cevatemre, Buse; Yılmaz, Veysel Taran; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-3781-6834; 0000-0002-2849-3332; AAH-5068-2021; L-6682-2018; AHD-2050-2022; L-7238-2018; 57193196674; 6603627015; 56422040600; 55693788600; 7006269202Metal-based chemotherapeutics such as cisplatin are widely used treatment of lung cancer which is the major cause of cancer-related mortality worldwide. Recent studies demonstrated that novel metal-based compounds have strong cytotoxic activity in a similar way as cisplatin. Therefore, metal-based compounds have been synthesized and investigated in order to determine their cytotoxic activities. It has been also reported curcumin, which has been derived from turmeric plant, has powerful cytotoxic effect on various cancer cell lines. In the light of these data, it has been investigated the cytotoxic effects of combination of curcumin (0.78-100 mu M) and palladium (II) 5,5-diethylbarbiturate complex with bis(2-pyridylmethyl)amine [Pd(II) complex] (0.39-50 mu M) against non small lung cancer cell lines, A549 and H1299. It has been found that combination of Pd(II) complex and curcumin enhanced the cytotoxic activity and apoptotic cell death at 48 h, compared to single use of each agent, only in H1299 cell line (combination index <1). Apoptosis was evident by annexin v staining positivity, increased caspase 3/7 activity and the presence of pyknotic nuclei. Pro-apoptotic genes of TNFRSFIOA and HRK were found to be involved in apoptotic cell death. In conclusion, the application of this combination may be regarded as a novel and effective approach for the treatment of lung cancer due to its promising cytotoxic and apoptotic effect.Publication Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress-induced apoptosis(Springer, 2019-10-26) İçsel, Ceyda; Yılmaz, Veysel T.; Cevatemre, Buse; Aygün, Muhittin; Ulukaya, Engin; İÇSEL YILMAZ, CEYDA; YILMAZ, VEYSEL TURAN; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-2849-3332; L-7238-2018; AAI-3342-2021A series of the structurally related platinum(II) saccharinate (sac) complexes with alkylphenylphosphines, namely cis-[Pt(sac)(2)(PPh2Me)(2)]center dot DMSO (1), cis-[Pt(sac)(2)(PPhMe2)(2)] (2), cis-[Pt(sac)(2)(PPh2Et)(2)] (3), and cis-[Pt(sac)(2)(PPhEt2)(2)]center dot 2DMSO (4), were synthesized and fully characterized; their structures were determined by X-ray crystallography. All the complexes were investigated for their anticancer potentials on three human cancer cells including A549 (lung), MCF-7 (breast), and HCT116 (colon) in addition to a noncancerous human bronchial epithelial cells (BEAS-2B). Specifically, 1 and 3 showed significant cytotoxic effects against MCF-7 and HCT116 cell lines in comparison to cisplatin, and were considered as the most potent ones in the series. The cytotoxic complexes were found to cleave DNA efficiently. In addition, the binding interactions of the complexes with DNA were confirmed by enzyme inhibition and molecular docking studies. Complexes 1 and 3 were capable of inducing apoptosis and arrested the cell cycle at the DNA synthesis (S) phase in MCF-7 cells. Furthermore, 1 and 3 caused the excessive generation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and double-strand DNA breaks.Item Differential cytotoxic activity of a novel palladium-based compound on prostate cell lines, primary prostate epithelial cells and prostate stem cells(Public Library Science, 2013-05) Frame, Fiona M.; Pellacani, Davide; Walker, Hannah F.; Mann, Vincent M.; Simms, Matthew S.; Stower, Michael J.; Maitland, Norman J.; Ulukaya, Engin; Cevatemre, Buse; Yılmaz, Veysel Turan; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-2849-3332; K-5792-2018; L-7238-2018; 6602927353; 55693788600; 7006269202The outcome for patients with advanced metastatic and recurrent prostate cancer is still poor. Therefore, new chemotherapeutics are required, especially for killing cancer stem cells that are thought to be responsible for disease recurrence. In this study, we screened the effect of a novel palladium-based anticancer agent (Pd complex) against six different prostate cancer cell lines, and primary cultures from seven Gleason 6/7 prostate cancer, three Gleason 8/9 prostate cancer and four benign prostate hyperplasia patient samples, as well as cancer stem cells selected from primary cultures. MTT and ATP viability assays were used to assess cell growth and flow cytometry to assess cell cycle status. In addition, immunofluorescence was used to detect gamma H2AX nuclear foci, indicative of DNA damage, and Western blotting to assess the induction of apoptosis and autophagy. The Pd complex showed a powerful growth-inhibitory effect against both cell lines and primary cultures. More importantly, it successfully reduced the viability of cancer stem cells as first reported in this study. The Pd complex induced DNA damage and differentially induced evidence of cell death, as well as autophagy. In conclusion, this novel agent may be promising for use against the bulk of the tumour cell population as well as the prostate cancer stem cells, which are thought to be responsible for the resistance of metastatic prostate cancer to chemotherapy. This study also indicates that the combined use of the Pd complex with an autophagy modulator may be a more promising approach to treat prostate cancer. In addition, the differential effects observed between cell lines and primary cells emphasise the importance of the model used to test novel drugs including its genetic background, and indeed the necessity of using cells cultured from patient samples.Item Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line(Elsevier, 2016-11-10) Ulukaya, Engin; Aydınlık, Seyma; Erkısa, Merve; Cevatemre, Buse; Sarımahmut, Mehmet; Dere, Egemen; Arı, Ferda; Uludağ Üniversitesi/Fen Edebiyet Fakültesi/Biyoloji Bölümü.; 0000-0001-5238-2432; 0000-0002-3127-742X; 0000-0003-2647-5875; 0000-0002-6729-7908; ABI-2909-2020; AAM-1001-2020; AHD-2050-2022; AAG-8288-2021; AAH-5068-2021; AAG-7012-2021; 57190280044; 57126208900; 55693788600; 44661687400; 6603627015; 24376085300Background: The outcome of triple negative breast cancer is still poor and requires improvement with better therapy options. Autophagy has recently been shown to play a role in anticancer drug resistance. Therefore, we investigated if the effectiveness of doxorubicin was augmented by the inhibition of autophagy. Methods: MDA-MB-231 was used as a model cell line for triple negative breast cancer and 3-methyladenine was used as an inhibitor of autophagy. Cells were treated with 0.46-1.84 mu M doxorubicin and 2.5-10 mu M 3-methyladenine for 48 h. Cell death mode was examined with M30 and M65 ELISA assays. ROS level and LDH activity was examined and the cellular acidic compartment of cells was monitored by acridine orange staining. The expression of various autophagy and apoptosis related proteins/genes were evaluated with Western blotting and RT-qPCR respectively. Results: Synergism was observed between the compounds (CI value < 1.0). RT-qPCR analysis revealed that the combination resulted in a down-regulation of autophagy-related genes. Moreover, the combination resulted in a different cell death modality, upregulating necroptosis-related genes. This suggests that the mode of cell death may switch from apoptosis to necroptosis, which is a more severe form of cell death, when autophagy is inhibited. These results were further confirmed at protein level by Western blotting. Conclusion: Inhibition of autophagy seems to sensitize triple negative breast cancer cells to doxorubicin, warranting further in vivo studies for the proof of this concept. General significance: Autophagy has a key role in drug resistance in MDA-MB-231 cells. Therefore combinatorial approaches may effectively overcome resistance.Item Evaluation of the molecular mechanisms of a palladium(II) saccharinate complex with terpyridine as an anticancer agent(Lippincott Williams & Wilkins, 2014-01) Kaçar, Ömer; Adıgüzel, Zelal; Çetin, Yüksel; Tarık, Ahmet Baykal; Açılan, Ceyda; Arda, Nazlı; Yılmaz, Veysel Turan; Ulukaya, Engin; Cevatemre, Buse; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; 0000-0002-2849-3332; K-5792-2018; L-7238-2018; 7006269202; 55693788600; 6602927353Metal-based compounds represent promising anticancer therapeutic agents. In this study, the mechanism of action of a novel metal-based drug, a palladium(II) (Pd) complex ([PdCl(terpy)](sac)2H(2)O, terpy=2,2':6',2 ''-terpyridine and sac=saccharinate), was elucidated. The tested compound induced cytotoxicity in nine different human cancer cell lines that originated from various organs, suggesting a broad spectrum of activity. The IC50 values were significantly higher for noncancerous cells when compared with cancer cells. We found that cells treated with the Pd(II) complex exhibited increased caspase 3/7 activities and condensed/fragmented nuclei, as demonstrated by nuclear staining and DNA laddering. Morphological features, such as cellular shrinkage and blebbing, were also observed, indicating that apoptosis was the primary mechanism of cell death. Pd(II) treatment induced DNA double-stranded breaks both in vitro and in vivo, potentially accounting for the source of stress in these cells. Although caspase 3/7 activities were elevated after Pd(II) treatment, silencing or using inhibitors of caspase 3 did not block apoptosis. Other molecules that could potentially play a role in Pd(II)-induced apoptosis, such as p53 and Bax, were also tested using silencing technology. However, none of these proteins were essential for cell death, indicating either that these molecules do not participate in Pd(II)-induced apoptosis or that other pathways were activated in their absence. Hence, this new molecule might represent a promising anticancer agent that exhibits cytotoxicity in p53-mutant, Bax-mutant, and/or caspase 3-mutant cancer cells.Item Fenretinid ve indol-3-karbinol kombinasyonunun meme kanseri hücre soyları üzerindeki sitotoksik/apoptotik etkilerinin araştırılması(Uludağ Üniversitesi, 2012) Cevatemre, Buse; Dere, Egemen; Uludağ Üniversitesi/Fen Bilimleri Enstitüsü/Biyoloji Anabilim Dalı.Günümüzde meme kanseri hastalarının durumları, kliniğe yeni kemoterapi rejimleri girmesine rağmen halen tatmin edici değildir.Bu nedenle, meme kanseri hastalarında kullanılabilecek yeni yaklaşımlar gerekmektedir. Bu çalışmada, sentetik bir retinoid olan fenretinid (4-HPR) ile brokoli ve lahana gibi bitkilerde doğal bir bileşik olarak bulunan indol-3-karbinol'ün (I3C), MCF-7 (östrojen reseptör pozitif) ve MDA-MB-231 (östrojen reseptör negatif) hücre soyları üzerindeki sitotoksik aktiviteleri araştırılmıştır. MCF-7 ve MDA-MB-231 hücrelerinde, 4-HPR ve I3C kombinasyon tedavisinin apoptozisi indükleyerek, bileşiklerin yalnız başlarına kullanımına kıyasla daha güçlü bir sitotoksik aktiviteye neden olduğu bulunmuştur. Sonuç olarak, kombinasyon tedavisinin, insan meme kanseri tedavisinde kullanılabileceği öngörüsüyle in vivo deneylerin yapılması gerekmektedir.Publication Is vitamin D 3 has any effect on the proliferation of colorectal cancer (HCT116) cells?(Wiley, 2015-07-01) Küçükhüseyin, O.; Temoçin, O.; Turan, S.; Ersez, M. Süleymanoğlu; Çelik, D.; Cevatemre, Buse; Ulukaya, Engin; Kuruca, S.; Yaylım, I.; Cevatemre, Buse; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi; 0000-0003-4875-5472; CIJ-5092-2022; K-5792-2018Item The M30 assay does not detect apoptosis in epithelial-derived cancer cells expressing low levels of cytokeratin 18(Sage Publications LTD, 2015-08-01) Frame, Fiona M.; Cevatemre, Buse; Ulukaya, Engin; Sarımahmut, Mehmet; Oral, Arzu Yilmaztepe; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; 0000-0003-4875-5472; 0000-0003-2647-5875; 0000-0003-0463-6818; AHD-2050-2022; K-5792-2018; AAG-8288-2021; A-5841-2017; 55693788600; 6602927353; 44661687400; 23091316500The primary aim of this study was to compare measurement of apoptosis by M30 immunoreactivity (a biomarker for apoptosis) to other apoptosis assays (morphological assessment of nuclei, Annexin-V-FITC staining, DNA fragmentation and PARP cleavage) in vitro. Caspase-cleaved cytokeratin 18 (M30, ccK18) is only produced in epithelial cells and is regarded as a pharmacodynamic biomarker of apoptotic cell death because it is released from cells during apoptosis induced by chemotherapeutic agents. However, we have observed false negative results using this assay in clinical samples. Therefore, we tested its ability to accurately detect apoptosis in a panel of lung cancer cell lines with a range of clinically approved chemotherapeutic drugs. Three different non-small cell lung cancer (NSCLC) cell lines (A549, H1299, PC3) were used to correlate M30 levels with alternate apoptosis assays. Following successful induction of apoptosis, the A549 cell line showed an increase in M30 levels along with other well-known features of apoptosis, whilst H1299 and PC3 cell lines did not show an increase in M30 levels, even when apoptosis was detected by other means. Further analysis showed that H1299 and PC3 cell lines expressed much lower levels of cytokeratin 18 protein compared to the A549 cell line. Our results suggest that reliable detection of apoptosis via the M30 assay only works when sufficient levels of cytokeratin 18 are present in the cells. This means that the M30 assay may result in false negative results for apoptosis, and as such, the ELISA should be used in conjunction with other assays.Item M30 assay may not be an accurate method for apoptosis in the cancer cells expressing low level of cytokeratin(Elsevier, 2014-07) Cevatemre, Buse; Arı, Ferda; Sarımahmut, Mehmet; Oral, Arzu Yılmaztepe; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0003-0463-6818; K-5792-2018; A-5841-2017Item Palladium(II) and platinum(II ) saccharinate complexes with bis(diphenylphosphino)methane/ ethane: synthesis, S-phase arrest and ROS- mediated apoptosis in human colon cancer cells(Royal Society of Chemistry, 2018-07-24) Aygün, Muhittin; Alper, Pınar; Ulukaya, Engin; İcsel, Ceyda; Yılmaz, Veysel Turan; Cevatemre, Buse; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-2717-2430; 0000-0002-2849-3332; AAI-3342-2021; L-7238-2018; AHD-2050-2022; 55551960400; 56441123900; 55693788600New neutral [M(sac)(2)(diphos)] and cationic [M(diphos)(2)](sac)(2) complexes, where M = Pd-II or Pt-II, sac = saccharinate, and diphos = 1,1-bis(diphenylphosphino)methane (dppm) or 1,2-bis(diphenylphosphino)ethane (dppe), were synthesized and structurally characterized. The anticancer activity of the complexes was investigated against MCF-7 (breast), A549 (lung), HCT116 (colon), DU145 (prostate) cancer and BEAS-2B (normal bronchial epithelial) cells. Neutral Pt-dppm (2) and Pd-dppe complexes (5) did not show any biological activity. The cationic Pd-dppe (7) complex displayed antiproliferative activity, while the rest of the complexes exhibited potent cytotoxicity compared with cisplatin. The active Pd(ii)/Pt(ii) complexes were then included in further studies including interaction with DNA/HSA, nuclease activity, cellular uptake and lipophilicity. The potent complexes induced the apoptotic cell death as probed through annexin V positivity and caspase activation. Mechanistic studies on HCT116 cells showed that the complexes cause cell cycle arrest at the DNA synthesis (S) phase and excessive generation of reactive oxygen species (ROS), damaging to both mitochondria and DNA.Item A palladium(II)-saccharinate complex of terpyridine exerts higher anticancer potency and less toxicity than cisplatin in a mouse allograft model(Lippincott Williams & Wilkins, 2017) Çetin, Yüksel; Adıgüzel, Zelal; Polat, Hivda Ulbeği; Akkoç, Tolga; Taş, Arzu; Çelik, Gökalp; Çarıkçı, Barış; Ulukaya, Engin; Açılan, Ceyda; Yılmaz, Veysel T.; Cevatemre, Buse; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-2849-3332; L-7238-2018; AHD-2050-2022; 55693788600; 56441123900The main aim of this study is to assess the safety and antitumor efficacy of a palladium(II) (Pd)-saccharinate complex with terpyridine. To characterize the Pd(II) complex in vitro, its cytotoxicity was evaluated using a water-soluble tetrazolium salt cell viability assay and the mechanism of cell death was assessed by DNA fragmentation/condensation and live cell imaging analyses. The antitumor efficacy and safety of the Pd(II) complex in-vivo were examined by analyzing reduction in tumor size, changes in body and organ weight, histopathological analysis of liver, kidney, and tumor sections, and biochemical analysis of serum in C57BL/6 mice. Our results showed that the Pd(II) complex was more cytotoxic to cancer cells than noncancer cell lines and caused cell death through apoptotic pathways. The treatment of the Pd(II) complex in tumor-bearing mice effectively reduced the tumor size at half the dose used for cisplatin. The Pd(II) complex appeared to exert less liver damage than the cisplatin-based complex on changes in the hepatic enzymes levels in the serum. Hence, the complex appears to be a potential chemotherapeutic drug with high antitumor efficacy and fewer hepatotoxic complications, providing an avenue for further studies.