Papers by Prof. Dr. Mine Ergüven
Anadolu BİL Meslek Yüksekokulu Dergisi, Mar 31, 2019
Kronik myeloid losemi (KML) losemilerin yaklasik dortte birini olusturur ve her 100.000 kisiden 1... more Kronik myeloid losemi (KML) losemilerin yaklasik dortte birini olusturur ve her 100.000 kisiden 1 veya 2’sinde bu hastalik gorulur. Diyetten elde edilen ya da bobrekte, karacigere ve beyindeki lizin ve metioninden endojen olarak sentezlenen bir yardimci faktor olan L-karnitin (LK), uzun zincirli yagli asitlerini (YA’lar), sitrik asit dongusu uzerinden ATP uretimi icin mitokondriyal matrikse tasir. YA’lerinin blokajina bagli olan tedavi uygulamalari ve LK seviyelerindeki dusus, kanser gerilemesine yol acar. Akut miyeloid losemi (AML) dahil olmak uzere cesitli kanser tiplerine tek olarak veya kombinasyon halinde LK uygulanmasi, apoptozun baslatilmasi yoluyla inhibisyon etkisi gosterir. Bununla birlikte LK uzerine, kansere neden oldugu ve kanser hucrelerini uygulanan kemoterapi ve/veya radyoterapi gibi kanser tedavilerinin verdigi zarardan korudugu hakkinda yayinlanmis bazi tartismali calismalar da bulunmaktadir. Bu derlemedeki amacimiz LK’nin etkilerini genel kanser semasi ile birlikte KML yonunden tekrar degerlendirmekti. Diger LK baz alinarak yapilan deneysel ve klinik calismalarin analizleri ve analiz yorumlarina yer verilerek yaptigimiz bu derlemenin sonunda, LK’nin gida takviyesi olarak alinirken veya zayiflamak icin kullanilirken veya tek basina ve/veya coklu kanser tedavilerinde adjuvant terapi ajani olarak kullanilirken LK’nin plazma konsantrasyon seviyeleri, apoptotik ve anti-apoptotik etkileri ile kanserojen olabilen metabolitleri goz onune alinarak kanser olusturma riskine karsi dikkatli olunmasi gerektigi sonucuna varildi.
Acta Neurobiologiae Experimentalis, 2021
Fasting, anticholinergics, and seizures affect c-fos activation in the brain. Additionally, antim... more Fasting, anticholinergics, and seizures affect c-fos activation in the brain. Additionally, antimuscarinic treated fasted animals develop convulsion soon after re-feeding. Therefore, we assessed whether c-fos expression changes in fed, fasting, and refed animals and how scopolamine treatment affects these changes. We further assessed whether there is a change in c-fos expression after convulsions. For this purpose, BALB/c mice fasted for 1, 3, 6, 12, 24 and 48 h periods were used. The animals were treated with saline or scopolamine. Half of the animals treated with saline or scopolamine were given food 20 min after injection. All animals were observed for development of convulsions for 30 min. At the end of this period, the brains of all animals were removed, and the percentage of c-fos active cells in the hypothalamus was determined immunohistochemically. Convulsions occurred within 1-48 h of fasting, after scopolamine treatment and re-feeding. Compared to fed animals, c-fos expression was not significantly changed in those undergoing different fasting periods, but significantly decreased after 12 h fasting. After animals were allowed to eat, c-fos activation significantly increased in the 1, 3, 6 and 12 refed-saline groups and decreased in the 48 refed-saline group. Scopolamine treatment in 1-24 h fasted animals increased c-fos expression, but decreased in 48 h fasted animals. Whereas convulsion development in scopolamine-treated 3, 6, 12 and 24 h refed animals suppressed c-fos expression. These results demonstrate that re-feeding and scopolamine treatment induces neuronal activity in the hypothalamus, while scopolamine induced convulsions after food intake suppressed the c-fos activity.
Physiology International, 2017
It has been reported that changes in cytokine levels affect mitochondrial functions, levels of hy... more It has been reported that changes in cytokine levels affect mitochondrial functions, levels of hypoxia-inducible factor α (HIF-1α), and tissue damage during sepsis. We aimed to investigate the effects of simvastatin pretreatment on mitochondrial enzyme activities, and on levels of ghrelin, HIF-1α, and thiobarbituric acid reactive substances (TBARS) in kidney tissue during sepsis. Rats were separated into four groups, namely, control, lipopolysaccharides (LPS) (20 mg/kg), simvastatin (20 mg/kg), and simvastatin + LPS. We measured the levels of mitochondrial enzyme activities and TBARS in the kidney using spectrophotometry. The histological structure of the kidney sections was examined after staining with hematoxylin and eosin. Tumor necrosis factor α (TNF-α), IL-10, HIF-1α, and ghrelin immunoreactivity were examined using proper antibodies. In tissue, TNF-α (p < 0.01) and HIF-1α (p < 0.05) levels were increased in the simvastatin + LPS and LPS groups. TBARS levels were higher i...
Connective Tissue Research, 2017
Background: 1,25-dihydroxyvitamin D 3 (1,25-OH D 3) plays an important role in mineralized tissue... more Background: 1,25-dihydroxyvitamin D 3 (1,25-OH D 3) plays an important role in mineralized tissue metabolism, including teeth. However, few studies have addressed its role in odontoblastic differentiation of human dental pulp-stem cells (hDPSCs). Aim: This study aimed to understand the influence of various concentrations of 1,25-OH D 3 on the proliferation capacity and early dentinogenesis responses of hDPSCs. Materials and Methods: hDPSCs were obtained from the impacted third molar teeth. Monolayer cultured cells were incubated with a differentiation A c c e p t e d M a n u s c r i p t 2 medium containing different concentrations of 1,25-OH D 3 (0.001, 0.01, and 0.1 µM). All groups were evaluated by S-phase rate [immunohistochemical (IHC) bromodeoxyuridine staining], STRO-1 and dentin sialoprotein (DSP)+ levels (IHC), and alkaline phosphatase (ALP, enzyme-linked immunosorbent assay) levels. Results: The number of cells that entered the Sphase was determined to be the highest and lowest in the control and 0.001 µM 1,25-OH D 3 groups, respectively. The 0.1 µM vitamin D 3 group had the highest increase in DSP+ levels. The highest Stro-1 levels were detected in the control and 0.1 µM 1,25-OH D 3 groups, respectively. The 0.1 µM 1,25-OH D 3 induced a mild increase in ALP activity. Conclusions: This study demonstrated that 1,25-OH D 3 stimulated odontoblastic differentiation of hDPSCs in vitro in a dose-dependent manner. The high DSP + cell number and a mild increase in ALP activity suggest that DPSCs treated with 0.1 μM 1,25-OH D 3 are in the later stage of odontoblastic differentiation. The results confirm that 1,25-OH D 3 added cocktail medium provides a sufficient microenvironment for odontoblastic differentiation of hDPSCs in vitro.
Nitric Oxide, 2007
1st International Conference on Nitric Oxide and Cancer -- NOV 26-28, 2007 -- Paris, FRANCEWOS: 0... more 1st International Conference on Nitric Oxide and Cancer -- NOV 26-28, 2007 -- Paris, FRANCEWOS: 00025083600006
Fertility and Sterility, 2018
(ICSI), assisted hatching, number of embryos transferred, and blastocyst transfer. A subgroup ana... more (ICSI), assisted hatching, number of embryos transferred, and blastocyst transfer. A subgroup analysis of patients with polycystic ovary syndrome (PCOS) as their only infertility diagnosis was performed using the same model. RESULTS: Our cohort included 8,430 patient cycles with elevated AMH and 2,186 patient cycles with ultrahigh AMH. Compared with women with elevated AMH, women with ultrahigh AMH were younger (31.1 vs 31.9 years, P<0.0001), more likely to be nulliparous (86.6% vs 83.2%, P¼0.0002), and were almost twice as likely to carry the diagnosis of PCOS (67.5% vs 37.5%, P<0.0001). Women with ultrahigh AMH required less gonadotropins (1,688 vs 1,950 IU, P<0.0001) and had more oocytes retrieved (20 vs 18, P<0.0001), but they had higher rates of cycle cancellation due to risk of ovarian hyperstimulation syndrome (OHSS) (11.5% vs 5.5%, P<0.0001). After adjusting for covariates, the odds of live birth were significantly lower for women with ultrahigh AMH than for those with elevated AMH (OR 0.85, 95% CI 0.75-0.97). Similar findings were observed in the subanalysis of only PCOS patients. CONCLUSIONS: Compared with women with elevated AMH, women with ultrahigh AMH (R10 ng/ml) are more likely to carry the diagnosis of PCOS. Ultrahigh AMH patients require less gonadotropin stimulation and have a higher oocyte yield; however, they are more likely to have cycle cancellation due to concern for OHSS, and they have significantly lower odds of live birth. We conclude that with elevated AMH, more is not always better for patient outcomes. References: 1. Piltonen et al. Serum anti-mullerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovarian syndrome. Hum Reprod 2005 Jul; 20(7):1820-6. 2. Xi et al. Correlation of serum anti-mullerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients.
DergiPark (Istanbul University), Jun 1, 2015
Endometrial cancer is the most common gynaecological malignant disease. Despite of some arguments... more Endometrial cancer is the most common gynaecological malignant disease. Despite of some arguments about the preference of herbal medicine to pharmaceutical drugs, because of their minimal side effects herbal medicine is proven to be effective as a single application and/or an adjuvant therapy. Rosa agretis Savi (R. agretis Savi) which belongs to Rosaceae family has been used traditionally to treat allergy, antiatopic dermatitis, and some inflammatory diseases, is commonly studied. Anti-oxidant activity is also reported. The present study was undertaken to investigate the in vitro anticancer activity of R. agrestis parts (leaves, flowers) at endometrium cancer. Extracts in a concentration of 1 µg/ml to 200 µg/ml from leaves and flowers were tested on human endometrium cell line named Ischikawa for 72 h. Cell proliferation (total cell number) and apoptotic index (flow cytometry) were evaluated for 72 h. All the results were statistically analyzed using the independent Student's t-test. All extracts decreased cell number and increased apoptotic index with dead cells in concentration and time dependent manner (p<0.05). When the efficiency of flowers was compared with leaves, it's clearly seen that flowers were the most effective as an anticancer agent. Besides, their effects were seemed mild in comparison to positive control as an antineopastic agent lithium chloride (LiCl). In conclusion, our study showed for the first time that R. agrestis, regardless of leaves and flowers, possessed an anticancer effect on human endometrium cells in vitro.
DergiPark (Istanbul University), Jun 1, 2011
Mortalitesi en yüksek jinekolojik kanser olan over kanserinin tedavisindeki asıl problem nüks ve ... more Mortalitesi en yüksek jinekolojik kanser olan over kanserinin tedavisindeki asıl problem nüks ve kemoterapi direncidir. Kanser dokusunda, patogenezisden sorumlu tutulan, artmış büyüme potansiyeline sahip, uzun ömürlü hücre popülasyonu kanser kök hücreleri (KKH) olarak adlandırılırlar. KKH'lerinin kemo-rezistans ve agresif tekrarlayan tümörlerden sorumlu olduğu düşünülmektedir. Normal kök hücreden farklılaşarak kanser dokusunu oluşturan bu hücreler in-vitro koşullarda Multisellüler Tümör Sferoid Model (MTS) kullanılarak izole edilmektedirler. Bu çalışmada yüksek anti-tümör aktivitesine sahip, deoksisitidin analoğu Gemcitabine (2′2′-difluorodeoxycytidine, Gemzar®)'nin KKH'leri üzerinde anti-apoptotik etkileri incelenmiştir. Yöntem ve Gereç: MDAH-2774 insan over kanseri hücre hattından üç boyutlu hücre kültürü ile KKH izolasyonu yapılmış ve sferoidler Gemcitabine ile etkileştirilmiştir. 24. ve 96. saatlerde ilaçla etkileşen hücrelerdeki apoptotik değişiklikler p53, bcl-2, caspase-3 immunoreaktivitesiyle değerlendirilmiştir. Bulgular: p53 immunoreaktivitesi açısından Gemcitabine uygulanan grupta 24. ve 96. saatlerde artış görülmektedir. 24. saatlerde Gemcitabine uygulanan grupta bcl-2 immunoreaktivitesi azalmışken, 96. saatte 24. saate oranla bcl-2 belirgin artmıştır. Caspase-3 immunoreaktivitesi 24/96 saat arasında her iki grupta azalırken, 96. saatte Gemcitabine grubunda caspase-3'te azalma görülmüştür. Sonuç: p53 immunoreaktivitesinde artış ile bcl-2'deki azalma ilaç etkinliğinin bu apoptotik yolakları kullanarak gerçekleştiğini düşündürürken, caspase-3'de beklenen artışın olmaması caspase yolağının kullanılmadığını düşündürmektedir. Bugüne kadar ilaç duyarlılık testleri ve KKH üzerine etki mekanizmaları araştırma deneyleri tek tabaka hücre kültürleri ile değerlendirilmiştir. Bu araştırmaların KKH izolasyon tekniği kullanılarak değerlendirilmesi uygun olacaktır.
Türkiye klinikleri tıp bilimleri dergisi, 2011
The aim of this study was to eva lu a te and com pa re in vit ro bi o com pa ti bi lity and poly(... more The aim of this study was to eva lu a te and com pa re in vit ro bi o com pa ti bi lity and poly(glyco lic acid) (PGA) and poly(lac ti de-co-glyco li de acid) (PLGA) on tu mo ri ge nic and non-tu mo ri genic ma tu re sphe ro ids. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : This is an in vit ro ex pe ri men tal study. Tu mo ri ge nic (C6 glio ma, SH-SY5Y, MDAH2774, MCF-7) and non-tu mo ri ge nic cells [CRL11372, pri mary os te ob lasts (MCPO)] as well as the ir ma tu re sphe ro ids we re cul tu red alo ne as a con trol gro up as well as in combination with PGA and PLGA. To tal cell num bers, bro mo de ox yu ri di ne la be ling in dex (BrDU-LI), apop to sis, morp ho logy, and ul tras truc tu re we re eva lu a ted. R Re e s su ul lt ts s: : PGA and PLGA sig ni fi cantly dec re a sed the number of SH-SY5Y and C6 gli o ma cells; MDAH 2774 cells al so dec re a sed, but not sig ni fi cantly (p> 0.05). Low BrDU-LI (p< 0.05) with a high le vel of apop to sis (p< 0.05) at C6 gli o ma and a high le vel of BrDU-LI (p< 0.05) with a low le vel of apop to sis at MDAH2774 (p< 0.01) we re noted. The se bi o poly mers mostly dec re a sed the num ber of CRL-11372 cells (p< 0.05), but in di ca ted an in cre a sed apop to sis (p< 0.01) and sig ni fi cant BrDU-LI (p< 0.05). Bi o poly mers in du ced chro ma tin con den sa ti on (typi cal apop to tic ul tras truc tu re) and va cu oli za ti on pri ma rily at SH-SY5Y sphe ro ids but ra rely at MDAH-2774 sphe ro ids. This apop to tic ul tras tuc tu re was most of ten ob ser ved at MCPO sphe ro ids. PLGA and PGA in du ced si mi lar BrDU-LI dec re a ses among tu mo ri ge nic sphe ro ids (p< 0.05), alt ho ugh this dec re a se was gre a ter at MCF-7 (p< 0.05) in the PGA group. PGA pri ma rily dec re a sed BrDU-LI at CRL 11372 (p< 0.05), alt ho ugh the dec re a se was al most iden tical to that at MCPO for the two bi o poly mers (p< 0.05). A sig ni fi cant at tach ment af fi nity was de ter mi ned at MDAH-2774 and C6 gli o ma sphe ro ids. C Co on nc c l lu u s si i o on n: : This study de mons tra ted the bi o com pa ti bi lity of PGA and PLGA at ma tu re sphe ro ids of tu mo ri ge nic and non-tu mo ri ge nic cell li nes, which chan ged accor ding to the cell type. K Ke ey y W Wo or rd ds s: : Polyg lyco lic acid; ma te ri als tes ting; sphe ro ids, cel lu lar Ö ÖZ ZE ET T A Am ma aç ç: : Bu ça lış ma da, po li(gli ko lik asit) (PGA) ve po li(lak tid-ko-gli ko lid) (PLGA)'in tü mö ri je nik ve non-tü mö ri je nik ma tür sfe ro id ler de bi yo u yum lu lu ğu nun de ğer len di ril me si ve kar şı laş tı rıl ma sı amaç landı. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Ça lış ma de ney sel ola rak plan lan dı. Tü mö ro je nik (C6 gli o ma, SH-SY5Y, MDAH 2774, MCF-7) ve non-tü mö ro je nik [CRL 11372, pri mer os te ob last (MCPO)] hüc re ler ve ol gun sfe ro id le ri tek ba şı na ve bi yo po li mer ler ile bir lik te kül tü re edil di. Top lam hüc re sa yı sı, bro mo de ok si u ri din işa ret leme in dek si (BrDU-LI), apop to tik in deks, mor fo lo ji ve ul tras trük tür de ğer len di ril di. B Bu ul l g gu u l la ar r: : PGA ve PLGA'nın en faz la SH-SH5Y ve C6 gli o ma hüc re sa yı la rı nı azalt tı ğı ve MDAH 2774 hüc re sa yı la rı nı daha az azalt tı ğı sap tan dı (p> 0.05). Dü şük BrDU-LI (p> 0.05) yük sek apop toz (p< 0.05) C6 gli o ma da ve yüksek BrDU-LI (p> 0.05) dü şük apop toz (p< 0.05) MDAH2774'de (p< 0.01) gö rül dü. Bu po li mer lerin hüc re sa yı sı nı en faz la CRL-11372 (p> 0.05) de azalt tı ğı an cak apop to zu (p< 0.01) BrDU-LI (p> 0.05) ar tır dı ğı saptan dı. Po li mer le rin kro ma tin bi ri ki mi ni (ti pik apop to tik in ce ya pı sı) ve va ku o li zas yo nu en faz la SH-SY5Y sfe ro id le rin de ve na dir ola rak da MDAH-2774 sphe ro id le rin de oluş tur du ğu gö rül dü. Bu apop to tik in ceya pı en faz la MCPO sfe ro id le rin de sap tan dı. PLGA ve PGA' nın tü mö ri je nik sfe ro id ler ara sın da BrDU-LI'de ben zer azal ma ya ne den ol du ğu (p> 0.05), an cak bu azal ma nın PGA' da ki MCF-7'de da ha faz la ol du ğu gö rül dü (p< 0.05). PGA' nın BrDU-LI 'i en faz la CRL 11372'de (p> 0.05) azalt tı ğı an cak bu azal ma nın MCPO' de her iki po li mer için he men he men ay nı ol du ğu sap tan dı (p> 0.05). Yük sek tu tun ma eği li mi MDAH-2774 ve C6 gli o ma sfe ro id le rin de gö rül dü. S So o n nu uç ç: : Bu ça lış ma PGA ve PLGA' nın tü mö ri je nik ve non-tü mo ri je nik ma tür sfe ro id ler de bi yo u yum lu ol du ğu nu ve bu özel lik le ri nin hüc re ti pi ne gö re de ğiş tiği ni gös ter miş tir. A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Po lig li ko lik asit; mal ze me le rin de nen me si; sferoidler, hücresel T Tu ur rk ki iy ye e K Kl li in ni ik kl le er ri i
Human Reproduction
Study question Does hyaluronidase (HAse) have possible negative or positive effects on cumulus ce... more Study question Does hyaluronidase (HAse) have possible negative or positive effects on cumulus cells (CCs) during oocyte denudation before ICSI by altering midkine (MK) levels? Summary answer Hyaluronidase inhibits the proliferation of CCs via the inhibition of MK activity which may result in poor embryo quality and low ICSI success. What is known already MK is abundantly expressed in ovarian follicles. MK secreted from the cumulus-granulosa cells that surround oocytes was shown to promote the cytoplasmic maturation of oocytes. This effect of MK could be mediated via its' anti-apoptotic effect and some other mechanisms. The removal of CCs during oocyte denudation (OD) is done in order to select and grade the oocytes before ICSI. HAse is applied for ICSI to break down hyaluronic acid, which is present at high levels in the cumulus-oocyte complex during OD. To date, there have only been a few reported cases of the toxic effects of hyaluronidase on oocytes. Study design, size, dura...
Human Reproduction, 2021
Is there any relationship between apoptosis rate and progesterone levels in terms of the degree o... more Is there any relationship between apoptosis rate and progesterone levels in terms of the degree of embryo quality and clinical pregnancy success? The cumulus cell apoptosis and progesterone levels measured at the hCG day were associated with embryo quality and clinical pregnancy success. The high rate of apoptosis at cumulus cells led to poor embryo development with the clinical pregnancy failure. It is prospective study carried out with 40 healthy women diagnosed as the male factor between September 2017 and April 2018. 40 healthy women aged between 27–38 and diagnosed as the male factor who were undergoing IVF participated the study. The cumulus cells were taken after denudation and cultured. The rate of the apoptosis were measured using with TUNEL method every 24 hours for 96 hours. In concominant with the apoptosis evaluation, the embryo progession and clinical pregnancy rate were also monitored. Progesterone levels taken at the hCG day were also measured. In this study, it was ...
Turkish Journal of Biochemistry
Objectives This study aimed to investigate whether a growth factor and a cytokine midkine (MK) ca... more Objectives This study aimed to investigate whether a growth factor and a cytokine midkine (MK) can be a new biomarker for the diagnosis and treatment of unexplained female infertility (UFI) cases. Methods Serum (S), follicle fluid (FF), and cumulus cells (CCs) of the patients aged 20–42 years, diagnosed with male factor (MF) and UFI were used. Patients underwent Intracytoplasmic Sperm Injection (ICSI). The Anti-Müllerian Hormone (AMH) and MK levels with other hormone levels (FSH, LH, E2, PRL, INHB, TSH), the oocyte and embryo qualities, the fertilization and pregnancy rates, and cumulus cells (Cell number and ultrastructure, apoptosis rate) were evaluated. Student-T-test was performed and p<0.05 was considered statistically significant. Results and Discussion The lowest numbers of CCs were found at UFI (p<0.05). The lowest apoptosis rate with the highest CC viability rate was evaluated at MF (p<0.05). The lowest AMH and MK levels (S, FF) were detected at UFI in comparison t...
Oncology Letters, 2016
Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels ... more Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels of differentiation growth factor midkine (MK) are increased in PCa. Cancer and/or the treatment process itself may lead to psychiatric disorders. Lithium chloride (LiCl) has anti-manic properties and has been used in cancer therapy; however, it has a queried safety profile. In addition, cancer stem cells are responsible for the heterogeneous phenotype of tumor cells; they are involved in progression, metastasis, recurrence and therapy resistance in various cancer types. The aims of the present study were to investigate the effect of different concentrations of LiCl on PCa stem cells (whether a shift from tumorigenic to non-tumorigenic cells occurs) and to determine if these results can be explained through changes in MK levels. Monolayer and spheroid cultures of human prostate stem cells and non-stem cells were incubated with low (1, 10 µM) and high (100, 500 µM) concentrations of LiCl for 72 h. Cell proliferation, apoptotic indices, MK levels and ultrastructure were evaluated. Cells stimulated with low concentrations showed high proliferation, low apoptotic indices, high MK levels and more healthy ultrastructure. Opposite results were obtained at high concentrations. Furthermore, stem cells were more sensitive to stimulation and more resistant to inhibition than non-stem cells. LiCl exhibited concentration-dependent effects on stem cell and non-stem cell groups. MK levels were not involved in the biphasic effect of LiCl; however, they were proportionally affected. To the best of our knowledge, the present study was the first to show the effect of LiCl on PCa stem cells through MK.
Neurological research, 2016
Glioblastoma (GBM), the most common primary tumour of the central nervous system, is characterise... more Glioblastoma (GBM), the most common primary tumour of the central nervous system, is characterised by a high malignancy and poor prognosis. The aims of this study were to investigate whether the combination of imatinib mesylate (IM) and lithium chloride (LiCl) exhibited a synergistic effect in treatment and to determine whether midkine (MK) affected the fate of this treatment in vitro. Monolayer and spheroid cultures of the T98G human GBM cell line were treated with an IM and LiCl combination for 72 h. The cell proliferation index, apoptotic index, cell cycle distribution, apoptotic and anti-apoptotic protein levels, and cAMP level as well as the cellular morphology and ultrastructure were evaluated. All applications inhibited cell proliferation and induced apoptosis. The most substantial decreases in cell proliferation and the caspase-3, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor-alpha (PDGFR-α), multidrug resistance protein-1 (MRP-1), aquapori...
Journal of Gynecologic Oncology, 2011
International Journal of Oncology, 2010
The purpose of the study was to investigate whether carvedilol has an antiproliferative effect al... more The purpose of the study was to investigate whether carvedilol has an antiproliferative effect alone and whether carvedilol provides an additive, synergistic or antagonistic effect on imatinib mesylate-induced cytotoxicity in both C6 glioma monolayer and spheroid culture. The C6 rat glioma chemoresistant experimental brain tumour cell line, that is notoriously difficult to treat with combination chemotherapy, was used both in monolayer and spheroid cultures. We treated C6 glioma cells with carvedilol alone and a combination of carvedilol and imatinib mesylate at a concentration of 10 μM. Following treatment, we evaluated cell proliferation index, bromodeoxyuridine labelling index (BrDU-LI), cell cycle distributions, apoptotic cell percentages, cAMP levels and three dimensional cell morphology at monolayer cultures. In addition BrDU-LI, volume and morphology of spheroids were also assessed. Carvedilol and imatinib mesylate alone reduced cell number, BrDU-LI, cAMP levels and spheroid volume. Carvedilol and imatinib mesylate arrested cells at G0/ G1 phase in a time-dependent manner and time-independent manner, respectively. Carvedilol increased apoptosis rate only at the 24th h, but imatinib mesylate did for all time intervals. Interestingly carvedilol, drug with well-known protective effect on mitochondria, induced severe mitochondria damage, and imatinib mesylate induced autophagy confirmed only by transmission electron microscopy. These results suggest that carvedilol showed antitumour activity against rat C6 glioma cells and a combination of carvedilol with imatinib mesylate resulted in enhanced in vitro antitumour activity.
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Papers by Prof. Dr. Mine Ergüven