Browsing by Author "Ulukaya, Engin"
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Item 4-(N-hydroxyphenyl)retinamide can selectively induce apoptosis in human epidermoid carcinoma cells but not in normal dermal fibroblasts(Taylor & Francis, 2001) Wood, E. J.; Ulukaya, Engin; Kurt, Ayberk; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; K-5792-2018; 6602927353; 36615287100The retinoid 4-(N-hydroxyphenyl)retinamide (4HPR, fenretinide) has both growth inhibitory and apoptosis-inducing effects on a number of cancer cell lines in vitro and in vivo and has been entered into a number of oncological trials. However, little is known about its mechanism(s) of action or its effects on normal cells such as fibroblasts. In this study, the effects of fenretinide on both epidermoid carcinoma cells of vulva (cell line A431) and normal human dermal fibroblasts, both as monolayers and also grown in 3D cell culture systems, have been investigated. The 3D cell culture system contained normal human fibroblasts embedded in a type I collagen gel with the carcinoma cells seeded on top of the collagen gel, which mimics the epidermoid carcinoma. Fenretinide significantly inhibited the rate of DNA synthesis of carcinoma cells, while there was little effect on fibroblasts on monolayers, at 10(-6)-10(-5) M, which are clinically attainable does. Fenretinide at 5 x 10(-6) M induced apoptosis characterised by cell shrinkage, membrane blebbing, nuclear condensation and/or fragmentation, and cell detachment in carcinoma cells, but not fibroblasts from monolayers. Fenretinide also reduced the viability of carcinoma cells in the 3D cell culture system without affecting fibroblasts. These data show that fenretinide may preferentially induce apoptosis in epidermoid carcinoma cells.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 Akciğer kanserlerinde dokudaki VEGFR-1 ve TRAILR-1 ekspresyonları ile serum solubl VEGFR-1 düzeylerinin tedaviye yanıtla ilişkilerinin incelenmesi(Uludağ Üniversitesi, 2004) Yılmaztepe, Arzu; Tokullugil, H. Asuman; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.Artmış Vasküler Endotelyal Growth Faktör (VEGF) ekspresyonu akciğer kanseri dahil çeşitli kanserlerde gözlenmiştir. Vasküler Endotelyal Growth Faktör-Reseptör 1 (VEGF-R1) de bu etkilerine aracılık eden reseptörlerden biridir. Solubl Vasküler Endotelyal Growth Faktör-Reseptör 1 (sVEGF-R1) tümör anjiyogenezinde önemli endotelyal regülatörlerden biridir. VEGF'nin başlattığı sinyal iletimi yolunda tamamen zıt etki gösterir. Yani VEGF'nin etkisini inhibe eder. Tümör nekrozis Faktör (TNF) aracılı apoptozis indükleyici ligand (TRAIL), reseptörleri olan TRAIL-R1 ve TRAIL-R2 aracılığıyla selektif olarak kanser hücrelerini apoptozise götürerek metastazların önlenmesi ile ilişkili olabilir. Biz çalışmamızda malign akciğer kanserli hastaların serum sVEGF-R1 düzeyleri ile benign akciğer hastalıklı ve sağlıklı bireylerin sVEGF-R1 düzeylerini karşılaştırdık. sVEGF-RVin tedavi ve survi ile olası ilişkisini saptamaya çalıştık. Ayrıca çalışmamızda akciğer kanser dokusunda VEGF-R1 ve TRAIL-R1 ekspresyon düzeylerini inceleyerek tedavi ve survi ile ilişkisini saptamaya çalıştık. Malign olgular 42 kişiden oluşurken benign ve sağlıklı kontrol grubumuz toplam 55 kişiden oluşmaktaydı. Serum sVEGF-RI düzeyleri ELISA metodu ile ölçüldü. Doku VEGF-R1 ve TRAIL-R1 ekspresyon düzeyleri ise immunohistokimyasal olarak değerlendirildi.Serum sVEGF-RI düzeyleri bakımından malign ve nonmalign olgular arasında anlamlı bir fark gözlenmedi (p>0.05). Tedavi öncesi ve sonrası sVEGF-RI düzeyleri karşılaştırıldığında anlamlı bir fark saptanmadı (p>0.05). Fakat sVEGF-R1 düzeylerinin progresyon gösteren grupta anlamlı olarak daha az olduğu saptandı. Ayrıca tedavi yanıtı ile sVEGF-R1 düzeyleri karşılaştırıldığında, sVEGF-R1 düzeylerinin hastalığın progresif veya stabil olması durumu ile anlamlı bir korelasyon gösterdiği bulundu (p<0.05). Doku VEGF-R1 ekspresyon seviyeleri açısından progresif hastalar ile stabil hastalar arasında anlamlı bir fark saptandı. Doku sVEGF-R1 düzeyleri progresif grupta artmış olarak bulundu. Sonuç olarak serum sVEGF-RI düzeylerinin, tedaviye yanıtı tahmin etmede klinisyenlere yardımcı bir parametre olabileceği kanısına varıldı.Item Anti-angiogenic effect of a palladium(II)-saccharinate complex of terpyridine in vitro and in vivo(Elsevier, 2016-09-05) İlkay, Elif Armutak; Gürel, Ebru Gürevin; Kıyan, Hülya Tuba; Dimas, Konstantinos; Aydınlık, Şeyma; Yilmaz, Veysel Turan; Ulukaya, Engin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Moleküler Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; 0000-0002-2849-3332; 0000-0002-2849-3332; ABI-2909-2020; L-7238-2018; K-5792-2018; 57190280044; 7006269202; 6602927353Anti-angiogenic activity of palladium (Pd) (II)-based complexes is unknown despite their quite powerful anticancer activity. This study was therefore carried out to evaluate both in vivo anti-angiogenic effect and in vitro cytotoxic activity of a Pd(II)-based complex. ([Pd(sac)(terpy)](sac).4H(2)O(sac = saccharinate and terpy = 2,2':6',2 ''-terpyridine)) on HUVEC cells. The anti-angiogenic activity of the complex was evaluated in vivo using the chick embryo chorioallantoic membrane (CAM) assay, tube formation assay and the cytotoxicity was screened using the MIT viability assays. The CAM treated with the complex (50 mu g/pellet) showed a strikingly high anti-angiogenic effect (score 1.1 +/- 0.2) compared to the positive controls cortisone, prednisone and (+/-)-thalidomide (e.g. (+/-)-thalidomide score 0.9 +/- 0.2) tested at the same concentration. Furthermore, the complex showed neither membrane toxicity nor irritation at the tested concentration. According to the MTT assays, the human umbilical vein endothelial cell (HUVEC) viability was inhibited in a dose-dependent manner at tested concentrations (1.56-100 mu M). Pd(II) complex also reduced the tube network at the lower dose than the compared with thalidomide. These results suggest that the Pd(II)-complex has strong anti-angiogenic activity, which adds an important feature to the previously-described anticancer activity of the complex.Item Anti-cancer activity of a novel palladium(II) complex on human breast cancer cells in vitro and in vivo(Elsevier, 2011-10) Dimas, Konstantinos; İkitimur, Elif İlkay; Ulukaya, Engin; Arı, Ferda; Yılmaz, Veysel T.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-6729-7908; 0000-0002-2849-3332; K-5792-2018; AAG-7012-2021; L-7238-2018; 6602927353; 24376085300; 7006269202Anti-cancer effects of a newly-synthesized palladium(II) complex, [Pd(sac)(terpy)](sac)center dot 4H(2)O (sac = saccharinate, and terpy = 2,2':6',2 ''-terpyridine), were tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. The Pd complex had a strong anti-growth effect in a dose- and time-dependent manner in vitro. This effect was also confirmed by the experiment performed on Balb/c mice in vivo. The IC50 values were 0.09 mu M for MDA-MB-231 and 3.05 mu M for MCF-7. It was also very effective in disrupting the formation of MDA-MB-231 tubules on matrigel, indicative of a putative anti-invasive activity. It induced apoptosis via the cell death genes of DR4 and DR5. In conclusion, this newly-synthesized Pd (II) complex represents a potentially active novel drug for the breast cancer treatment.Item Anti-cancer effect of a novel palladium (ii) complex by inducing apoptosis on ehrlich ascites carcinoma in balb/c mice(Int Inst Anticancer Research, 2014-10) Armutak, Elif; Sönmez, Kıvılcım; Akgün-Dar, Kadriye; Şennazlı, Gülbin; Kapucu, Ayşegül; Yiğit, Funda; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; K-5792-2018Item 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 Anticancer effect of a novel palladium-saccharinate complex of terpyridine by inducing apoptosis on ehrlich ascites carcinoma (EAC) in balb-C mice(International Institute of Anticancer Research, 2015-03) İkitimur-Armutak, Elif İlkay; Sönmez, Kıvılcım; Akgün-Dar, Kadriye; Şennazlı, Gülbin; Kapucu, Ayşegül; Yiğit, Funda; Ulukaya, Engin; Yılmaz, Veysel Turan; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; 0000-0003-4875-5472; 0000-0002-2849-3332; K-5792-2018; L-7238-2018; 6602927353; 56441123900Background/Aim: [Pd(sac)(terpy)](sac)•4H2O (sac=saccharinate and terpy=2,2′:6′,2-terpyridine) is newlysynthesized palladium(II) (Pd) complex. We investigated the antiproliferative and apoptotic effects of this complex on Ehrlich ascites carcinoma (EAC). Materials and Methods: EAC cells were administered to 33 Balb/c mice. Mice were divided randomly into four groups: control, cisplatin, Pd(II) complex and paclitaxel. Control group animals received 0.9% NaCl; other groups received treatments cisplatin, Pd(II) complex and paclitaxel on days 7 and 12. At day 14, animals were sacrificed. Expression of active caspase-3, p53 and proliferating cell nuclear antigen (PCNA) was investigated and apoptosis was evaluated by terminal deoxynucleotidyltransferase (TdT)-mediated nick-end labelling (TUNEL) technique. Results: Expression of p53 and PCNA were found to be decreased (p<0.0001), cells with active caspase-3 and TUNEL-positive cells were found to be increased (p<0.0001) in all treatment groups. Conclusion: Like cisplatin and paclitaxel, this Pd(II) complex has a strong anticancer activity against EAC by inducing apoptosis and suppressing proliferation in vivo.Publication Anticancer potential of albumin bound wnt/β-catenin pathway inhibitor niclosamide in breast cancer cells(Wiley-v C H Verlag Gmbh, 2021-08-06) Ari, Ferda; Erkisa, Merve; Pekel, Gonca; Buyukkoroglu, Gulay; Ulukaya, Engin; Erturk, Elif; ERTÜRK, ELİF; Arı, Ferda; Erkısa, Merve; Bursa Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; Bursa Uludağ Üniversitesi/Sağlık Hizmetleri Meslek Yüksekokulu.; 0000-0002-6729-7908; 0000-0002-3127-742X; 0000-0002-5089-6007; 0000-0003-4875-5472; K-5792-2018; N-6551-2019; JQI-3400-2023; AAM-1001-2020; IWM-5784-2023Albumin-based nanoparticle transport systems (nab-technology) are a new strategy in cancer treatment and we aimed to increase the effectiveness of Niclosamide using this technology. Niclosamide was bound with bovine serum albumin (BSA) by desolvation to yield nanoparticle albumin-bound Niclosamide (nab-Niclo). Nab-Niclo anticancer activity was assessed by proliferation, apoptosis and DNA damage analyses on breast cancer cells. The results implied that nab-Niclo was a more potent agent in the inhibition of cell viability than free Niclosamide and albumin. Flow cytometry analysis show that nab-Niclo triggered apoptosis by caspase and mitochondriadependent pathways in cells and nab-Niclo enhances apoptosis by induce DNA damage in cells. Overall results of this study showed that the nanoparticle form of Niclosamide is effective for breast cancer treatment, presenting a new treatment strategy that can be safe and effective for breast cancer patients.Item Antigrowth and apoptosis inducing effects of hypericum olympicum L. and hypericum adenotrichum spach. on lung cancer cells In vitro: Involvement of DNA damage(Wiley, 2015-12-18) Aztopal, Nazlıhan; Erkısa, Merve; Çelikler, Serap; Ulukaya, Engin; Arı, Ferda; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı.; 0000-0003-3118-8061; 0000-0002-6729-7908; 0000-0002-3127-742X; 0000-0002-4177-3478; L-6687-2018; AAG-7012-2021; K-5792-2018; AAV-4886-2020; AAM-1001-2020; AAH-2767-2021; 55853882900; 57126208900; 8234554800; 6602927353; 24376085300Hypericum species are used in different folk medicines and screened for their biological activity including cancer. We, therefore, evaluated the possible cytotoxic/apoptotic and genotoxic activities of Hypericum adenotrichum Spach. and Hypericum olympicum L. Antigrowth effect was screened in human lung cancer cell lines (A549 and PC3) by the ATP viability assay, while genotoxic activity was performed using the Comet assay. Histological and biochemical methods were utilized to elucidate the cell death mode. The results indicate that the crude methanol extracts of H. olympicum L. and H. adenotrichum have both antigrowth/cytotoxic and genotoxic activities on these cells in a dose dependent manner. These extracts clearly induced apoptosis in PC3 lung cancer cell lines. In this study, we report for the first time that the H. olympicum and H. adenotrichum exhibits potential cytotoxic and genotoxic activities in lung cancer cells as well as the apoptosis-inducing roles through DNA damage in PC3 cells. Practical ApplicationsMedicinal plants are used in traditional medicine worldwide and several have been screened for their anticancer properties, we evaluated the possible cytotoxic and genotoxic activities of the Hypericum adenotrichum and Hypericum olympicum, which are still used in Turkish folk medicine. H. adenotrichum Spach., an endemic species in Turkey, and H. olympicum L., which are known as kantaron and used traditionally for their wound healing and antiseptic properties. It was found that Hypericum species showed a significant growth-inhibiting effect on human lung cancer cells and induced apoptosis-like cell death by DNA damage in PC3 lung cancer cells. These species may have a potential as anticancer agents and inspire to new improvements for medicinal chemistry.Item Apoptosis-inducing effect of a palladium(II) complex-[PdCl(terpy)](sac)center dot 2H2O] on ehrlich ascites carcinoma (EAC) in mice(Int Inst Anticancer Research, 2016-04-28) İkitimur, Elif I. Armutak; Gürel, Ebru Gürevin; Yaylım, İlhan; İşbilen, Banu Başok; Şennazlı, Gülbin; Yüzbaşıoğlu, Gülay Öztürk; Sönmez, Kıvılcım; Çelik, Faruk; Küçükhüseyin, Özlem; Korkmaz, Gurbet; Zeybek, Şakir Ümit; Ulukaya, Engin; Yılmaz, Veysel T.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 0000-0002-2849-3332; K-5792-2018; L-7238-2018; 6602927353; 56441123900Background/Aim: New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac)center dot 2H2O] (sac= saccharinate, and terpy= 2,2':6',2 ''- terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo. Materials and Methods: 42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3 beta, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis. Results: Expression of p53, PCNA, Bcl-2 was found decreased (p< 0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p< 0.001) in all groups. The survivalrelated markers did not show any statistical difference in complex groups. Conclusion: The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel.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 Apoptosis-inducing effect of Usnea filipendula Stirt. in breast cancer cells in vitro(Elsevier, 2014-07) Sarımahmut, Mehmet; Çelikler, Serap; Arı, Ferda; Oran, Semra; Aztopal, Nazlıhan; Öztürk, S.; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0003-2647-5875; 0000-0002-6729-7908; 0000-0003-3118-8061; JCN-7113-2023; AAG-7012-2021; L-6687-2018; K-5792-2018Item Apoptosis-inducing effects of morinda citrifolia and doxorubicin on the Ehrlich ascites tumour in balb-c mice(Pergamon-Elsevier Science, 2009-09) Taşkın, E. İ.; Akgün, Kadriye Dar; Kapucu, Ayşegül; Osanç, Esma; Doğruman, Hüsniye; Eraltan, Hakan; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; K-5792-2018Item Apoptosis-inducing effects of morinda citrifolia l. and doxorubicin on the ehrlich ascites tumor in balb-c mice(Wiley, 2009-12) Armutak, Elif İlkay; Akgün, Kadriye Dar; Kapucu, Ayşegül; Osanç, Esma; Doğruman, Hüsniye; Eraltan, Hakan; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; K-5792-2018; 6602927353Morinda citrifolia L. (Noni) is, a herbal remedy with promising anti-cancer properties. However, its effects on various, cancers are to be investigated to make a firm conclusion before implementing it into the clinical practice. Therefore, we investigated the cytotoxic potential of noni on Ehrlich ascites tumor grown in female Balb-c mice and also combined it with I potent anti-cancer agent, doxorubicin One group received noni only (n = 8). another one doxorubicin (n. = 8). and the other one noni + doxorubicin (n = 8) for 14 days after the inoculation of cells. The control group (n = 7) received 0.9% NaCl only. We found that short and long diameters of the tumor tissues were about 40-50% smaller, compared to those in control group This anti-growth effect resulted from the induction of apoptosis, which was confirmed by the positive results from the Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) analysis and the active caspase-3 cells in tissues Apoptosis also confirmed by caspase-derived cytokeratin 18 elevation in serum of the treated groups. Further, the proliferation was decreased, which was immunohistochemically shown by the PCNA staining. We conclude that noni may be usefull in the treatment of breast Cancer either on its own or in combination with doxorubicin. Further studies are warranted to assess the dosage and safely of using noni fruit juice in conjuction with anti-cancer drugs against breast cancer.Item Apoptosis: Why and how does it occur in biology?(Wiley, 2011-08) Açılan, Ceyda; Yılmaz, Yusuf; Ulukaya, Engin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya.; K-5792-2018; 6602927353The literature on apoptosis has grown tremendously in recent years, and the mechanisms that are involved in this programmed cell death pathway have been enlightened. It is now known that apoptosis takes place starting from early development to adult stage for the homeostasis of multicellular organisms, during disease development and in response to different stimuli in many different systems. In this review, we attempted to summarize the current knowledge on the circumstances and the mechanisms that lead to induction of apoptosis, while going over the molecular details of the modulator and mediators of apoptosis as well as drawing the lines between programmed and non-programmed cell death pathways. The review will particularly focus on Bcl-2 family proteins, the role of different caspases in the process of apoptosis, and their inhibitors as well as the importance of apoptosis during different disease states. Understanding the molecular mechanisms involved in apoptosis better will make a big impact on human diseases, particularly cancer, and its management in the clinics.Item The ATP assay, but not the MTT assay, detects further cytotoxicity of the combination of anthracycline-based therapy with histone deacetylase inhibitor (valproic acid) in breast cancer cells(Walter De Gruyter, 2010) İlkay, Elif Armutak; Arı, Ferda; Ulukaya, Engin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.; 0000-0002-6729-7908; K-5792-2018; AAG-7012-2021; 24376085300; 6602927353Purpose: It has been investigated that whether or not the combination of valproic acid (a histone deacetylase inhibitor) with anthracycline-based chemotherapy (FEC: 5-fluorouracil+epirubicine+ cyclophosphamide) would change the cytotoxic effects of FEC in breast cancer cells. Methods: The effect of valproic acid and its combination with FEC has been tested on MDA-MB-231 and MCF-7 human breast cancer cell lines. Anti-growth effects of treatments were determined by the MTT and ATP assays, while the detection of apoptosis was performed by the caspase-cleaved cytokeratin 18 assay. Results: Valproic acid treatment had anti-growth effect on the cell lines used at clinically achievable dose (0.6 mM). According to the MTT assay, the combination of valproic acid with different doses (50-200% Test Drug Concentration) of FEC did not result in any significant change over FEC-only treatment in both cell lines. However, according to the ATP assay, there has been found that the combination of 100% Test Drug Concentration FEC with valproic acid yielded more efficacy compared to FEC-alone. FEC induced the apoptosis in MCF-7 cells but the addition of valproic acid to FEC did not enhance apoptosis. Conclusion: According to the ATP assay, the use of valproic acid at the clinically achievable dose (0.6 mM) with different doses of FEC further increased the cytotoxic effect of FEC. However, this effect was not observed in the MTT assay. A caution should therefore be taken on the evaluation of the cytotoxic effect of valproic acid in cell lines.Item BCL-2 proteininin apoptoz yolakları üzerine etkisinin incelenmesi(Uludağ Üniversitesi, 2007) Çolakoğulları, Mukaddes; Ulukaya, Engin; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Biyokimya Anabilim Dalı.Apoptoz, programlanmış hücre ölümü, organizmada fizyolojik süreçlerin yanı sıra çeşitli patolojilerin ortaya çıkışındaki mekanizmalarda da rol oynamaktadır. Apoptoz sürecindeki dengenin bozulması, hastalıkların ortaya çıkışını tetiklemektedir. Bu sürecin engellenmesinde Bcl-2 proteininin artan ekpresyonu önemli rol oynamaktadır. Bu çalışmada anti-apoptotik etkinliği bilinen Bcl-2 proteininin, Ultraviole (UV) irradyasyonu, α-keto isokaproik asit (KİKA) veya Staurosporine (SSP) ile indüklenen hücre ölümü sürecinde olası koruyucu etkinliğinin Bcl-2 proteinini aşırı eksprese eden Rat 1 fibroblastlar aracılığı ile incelenmesi hedeflenmiştir. Bu çalışmanın verilerine göre, UV-B irradyasyonu ile indüklenen Rat 1 fibroblastlarının ölümünde, Bcl-2 proteinin varlığı hücre ölümünden kısmen korumaktadır. UV-B’ye bağlı olan hücresel stres nedeniyle c-Jun N-terminal kinaz (JNK) enzimleri bifazik fosforilasyon ile aktive olmaktadır. Bcl-2’nin aşırı varlığı JNK’nin ikinci fosforilasyon dalgasında gecikmeye neden olmaktadır. D-JNK inhibitörünün kullanılması hücre yaşamı oranını arttırdığı gibi Bcl-2’nin kırılmasını da engellemiştir. Bu veriler, JNK ve Bcl-2 arasında dinamik bir etkileşim olduğuna işaret etmektedir. JNK enzimi, UV-B irradyasyonu sonucunda tetiklenen hücre ölümünde Bcl-2 fonksiyonunu düzenleyen üst yolakta yer alıyor görünmektedir. Ayrıca Bcl-2 proteini KİKA ve SSP ile indüklenen hücre ölümüne karşı Rat 1 fibroblastlarda kısmen koruyucu etki göstermiştir ve pan-kaspaz inhibitörü olan QVD’nin kullanımı hücre yaşam süresini uzatmıştır. Sonuçta bu çalışmadan elde ettiğimiz veriler, Bcl-2 proteininin UV irradyasyonu, KİKA ve SSP ile indüklenen Rat 1 fibroblast hücre ölümünde koruyucu etkili olduğunu desteklemektedir.