Browsing by Author "Bozkurt, E"

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    Gingival crevicular fluid and salivary resistin and tumor necrosis factor-alpha levels in obese children with gingivitis
    Dogusal, G; Afacan, B; Bozkurt, E; Sönmez, I
    Background: This study aimed to evaluate the levels of resistin and tumor necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid (GCF) and saliva of obese children with gingivitis. Methods: One-hundred and thirty children (65 obese and 65 normal weight; age range 8 to 12 years) were recruited for the study. The children were classified into four subgroups based on their body mass and periodontal status; 1) obese children with gingivitis (OG, n = 33); 2) obese children with healthy periodontium (OH, n = 32); 3) normal weight children with gingivitis (NWG, n = 32); 4) normal weight children with healthy periodontium (NWH, n = 33). Body mass index (BMI) percentile, probing pocket depth (PPD), gingival index (GI), and plaque index (PI) were recorded. Resistin and TNF-alpha were analyzed in GCF and saliva samples by ELISA. Results: (these children had higher BMI percentiles than normal weight children (p < 0.0001). PPD, GI, PI, GCF volume, GCF, and salivary resistin and TNF-alpha levels were similar between obese and normal weight children (P > 0.05). OG and NWG subgroups had significantly higher GI, PI, GCF volume, GCF resistin total amounts, and salivary resistin concentrations but lower GCF resistin and TNF-alpha concentrations than OH and NWH (P < 0.0001 for all). GCF resistin total amounts were positively correlated with GI, PI, and GCF TNF-alpha total amounts (P < 0.05). Conclusions: To our knowledge, this is the first study evaluated the levels of resistin in GCF and saliva of children. Obesity is not associated with GCF and salivary resistin and TNF-alpha levels in children in the presence of gingival inflammation.
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    Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines
    Atmaca, H; Bozkurt, E
    Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by -2.9, -3.7, -1.7, -1.7, -2.0 and -1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by -5.1, -2.0, -2.4, -3.1, -1.5, -2.0 and -2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer.
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    Effects of Galium aparine extract on the cell viability, cell cycle and cell death in breast cancer cell lines
    Atmaca, H; Bozkurt, E; Cittan, M; Tepe, HD
    Ethnopharmacological relevance: Galium species have been traditionally used for its anti-cancer, antioxidant, anti-inflammatory, antimicrobial and cardioprotective effects in the folk medicine. Galium aparine (GA) is a typical climbing plant growing widespread in Anatolia. Aim of the study: To investigate the potential anti-proliferative and apoptotic effect of GA methanol (MeOH) extract on MCF-7 and MDA-MB-231 human breast cancer cells and MCF-10A untransformed breast epithelial cells. Materials and methods: First, the extract was characterized by both liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) analyses. Then, cell viability and cell cycle distribution were investigated by XTT assay and PI staining by flow cytometry, respectively. Cell death was determined by Annexin V FITC/7-AAD staining. Results: A total of 14 major phytochemicals were identified by LC/Q-TOF/MS and 34 volatile compounds were determined by GC-MS. The extract was cytotoxic in both breast cancer cell lines in a concentration and time dependent manner and showed G1 block after 72 h extract treatment. However, it was not cytotoxic to MCF-10A breast epithelial cells. Flow cytometry analyses revealed that apoptosis was induced in MDA-MB-231 cells; however, necrosis was induced in MCF-7 cells. Conclusion: Our study suggests that GA MeOH extract may have potential anti-cancer effects against breast cancer cells without impairing normal breast epithelial cells. Ability to induction of non-apoptotic cell death besides apoptotic cell death by this complex plant-derived mixture may enable the killing of apoptosis resistant breast cancer cells but further studies should be conducted to investigate the bioavailability and metabolism of it in vivo. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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    Paclitaxel in combination with AT-101 induces apoptosis via supressing Bcl-2, bcl-XL, mcl-1 proteins in human breast cancer cells.
    Cakar, B; Gursoy, P; Atmaca, H; Kisim, A; Bozkurt, E; Uzunoglu, S; Sezgin, C; Sanli, UA; Karabulut, B; Uslu, R; Karaca, B
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    Trabectedin to induce mitochondrial membrane potential dissipation and reactive oxygen species generation in breast cancer cells.
    Atmaca, H; Bozkurt, E; Cakar, B; Surmeli, ZG; Uzunoglu, S; Uslu, R; Karaca, B
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    Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells
    Karaca, B; Atmaca, H; Bozkurt, E; Kisim, A; Uzunoglu, S; Karabulut, B; Sezgin, C; Sanli, UA; Uslu, R
    We investigated the effects of AT-101/cisplatin combination treatment on the expression levels of apoptotic proteins and epigenetic events such as DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzyme activities in OVCAR-3 and MDAH-2774 ovarian cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were performed. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. DNMT and HDAC activities were evaluated by ELISA assay and mRNA levels of DNMT1 and HDAC1 genes were quantified by qRT-PCR. Combination of AT-101/cisplatin resulted in strong synergistic cytotoxicity and apoptosis in human ovarian cancer cells. Combination treatment reduced some pivotal anti-apoptotic proteins such as Bcl-2, HIF-1A, cIAP-1, XIAP in OVCAR-3 cells, whereas p21, Bcl-2, cIAP-1, HSP27, Clusterin and XIAP in MDAH-2774 cells. Among the pro-apoptotic proteins, Bad, Bax, Fas, phospho-p53 (S46), Cleaved caspase-3, SMAC/Diablo, TNFR1 and Cytochrome c were induced in OVCAR-3 cells, whereas, Bax, TRAILR2, FADD, p27, phospho-p53 (S46), Cleaved caspase-3, Cytochrome c, SMAC/Diablo and TNFR1 were induced in MDAH-2774 cells. Combination treatment also inhibited both DNMT and HDAC activities and also mRNA levels in both ovarian cancer cells. AT-101 exhibits great potential in sensitization of human ovarian cancer cells to cisplatin treatment in vitro, suggesting that the combination of AT-101 with cisplatin may hold great promise for development as a novel chemotherapeutic approach to overcome platinum-resistance in human ovarian cancer.
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    Comparative analysis of XTT assay and xCELLigence system by measuring cytotoxicity of resveratrol in human cancer cell lines
    Atmaca, H; Bozkurt, E; Kisim, A; Uslu, R
    Objective: In vitro preliminary oncological and translational studies are mainly based on evaluating the cytotoxic effects of a specific compound on cultured cells. Resveratrol is a commercially available compound which is originally isolated from the roots of white hellebore and later from Polygonum cuspidatum. The objective of the study was to compare cytotoxicity data of Resveratrol from XTT end point assay with a real-time cell based xCELLigence system in terms of accuracy, sensitivity, speed and reproducibility in a panel of human cancer cell lines. Methods: XTT end point assay and real-time cell based xCELLigence system were used to evaluate cytotoxicity. Cytotoxicity results were verified by monitoring cells under phase-contrast microscope which were treated with IC50 values of resveratrol. Results: Resveratrol decreased cell viability in a time and concentration-dependent manner in all cancer cell lines when tested by both the XTT assay and xCELLigence system. Standard deviations of the xCELLigence data were found to be lower than the data from XTT assay. Conclusion: The data from this study strongly imply that xCELLigence system has higher precision, more enlightening and more reproducible than XTT end point assay.
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    AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells
    Yurekli, BS; Karaca, B; Kisim, A; Bozkurt, E; Atmaca, H; Cetinkalp, S; Ozgen, G; Yilmaz, C; Uzunoglu, S; Uslu, R; Saygili, F
    Purpose Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.
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    Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway
    Surmeli, Z; Gursoy, P; Erdogan, AP; Bozkurt, E; Atmaca, H; Uzunoglu, S; Sezgin, C; Sanli, UA; Uslu, R; Karaca, B
    The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells.
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    Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells
    Bozkurt, E; Atmaca, H; Kisim, A; Uzunoglu, S; Uslu, R; Karaca, B
    Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.
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    A potent enantiomer of gossypol, AT-101: Screening of anti-angiogenic protein targets in glioblastoma multiforme cells
    Surmeli, Z; Bozkurt, E; Karaca, B; Karabulut, B; Sezgin, C; Sanli, UA; Uslu, R
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    A diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells
    Atmaca, H; Bozkurt, E; Uzunoglu, S; Uslu, R; Karaca, B
    Trabectedin (Yondelis, ET-743), a semi synthetic tetrahydroisoquirioline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata. The objective of this study was to investigate whether trabectedin mediated apoptosis shows any diversity in human breast cancer cell lines with different genotypes. Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-RI/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bd-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells. Moreover, trabectedin treatment increased the generation of ROS in both breast cancer cells. We have shown that trabectedin causes selective activation of extrinsic and intrinsic apoptotic pathways in two genotypically different breast cancer cells. This preliminary data might guide clinicians to choose appropriate combination agents with trabectedin based on different molecular subtypes of breast cancer. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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    The evaluation of peri-implant sulcus fluid osteocalcin, osteopontin, and osteonectin levels in peri-implant diseases
    Cakal, OT; Efeoglu, C; Bozkurt, E
    Background: Peri-implant mucositis is an inflammation of the soft tissues surrounding an implant. Peri-implantitis refers to a process characterized by peri-implant bone loss along with an inflammation of the soft tissues. Osteocalcin, osteopontin, and osteonectin proteins are related to bone remodeling. The aim of the present study was to investigate peri-implant sulcus fluid (PISF) osteocalcin, osteopontin, and osteonectin levels in peri-implant mucositis and peri-implantitis. Methods: Fifty-two implants with peri-implantitis, 46 implants with peri-implant mucositis, and 47 control implants were included in the study. Clinical parameters including probing depth, modified sulcus bleeding index and modified plaque index were recorded. PISF osteocalcin, osteopontin, and osteonectin levels were analyzed by ELISA kits. Results: There were no significant differences in PISF osteocalcin, osteopontin, and osteonectin total amounts between healthy controls, peri-implant mucositis and peri-implantitis groups (P > 0.05). Probing depths were not correlated with PISF osteocalcin, osteopontin, and osteonectin levels in the study groups (P > 0.05). Conclusions: Soft tissue inflammation around dental implants does not cause a change in osteocalcin, osteopontin, and osteonectin levels in PISF. Also, peri-implantitis does not seem to give rise to an increase in PISF levels of osteocalcin, osteopontin, and osteonectin.
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    Enhancement of docetaxel efficacy by zoledronic acid pretreatment in docetaxel-resistant prostate cancer cells (PC-3/R and DU-145/R)
    Surmeli, Z; Bozkurt, E; Ozer, O; Atmaca, H; Kisim, A; Uzunoglu, S; Uslu, R; Karaca, B
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    Gingival crevicular fluid and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease
    Afacan, B; Öztürk, VÖ; Pasali, Ç; Bozkurt, E; Köse, T; Emingil, G
    Background Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is expressed as an adaptive response to hypoxia, mediates angiogenesis through the expression of vascular endothelial growth factor (VEGF) and can be induced by tumor necrosis factor-alpha (TNF-alpha). This study aimed to investigate the gingival crevicular fluid (GCF) and salivary HIF-1 alpha, VEGF, and TNF-alpha levels in periodontal health and disease. Methods A total of 87 individuals, 20 generalized aggressive periodontitis (G-AgP), 20 chronic periodontitis (CP), 26 gingivitis patients, and 21 periodontally healthy individuals, were included. Clinical periodontal parameters were recorded; GCF and salivary samples were collected; and HIF-1 alpha, VEGF, and TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Nonparametric tests were used for the statistical analyses. Results G-AgP and CP groups had significantly higher GCF HIF-1 alpha, VEGF, and TNF-alpha total amounts than gingivitis and healthy groups (P < 0.05). GCF HIF-1 alpha and TNF-alpha total amounts in gingivitis group were significantly higher than the healthy group (P < 0.05). GCF and salivary concentrations of biomarkers were similar in both periodontitis groups (P > 0.05). Salivary HIF-1 alpha concentrations in gingivitis group were significantly higher than G-AgP and healthy groups (P < 0.05). GCF HIF-1 alpha, VEGF, and TNF-alpha total amounts were positively correlated with the site-specific clinical periodontal parameters and with each other (P < 0.05). Conclusions HIF-1 alpha is detectable in GCF and saliva of periodontally diseased and healthy individuals, and the GCF levels of the biomarker can be affected by disease status. Increased GCF HIF-1 alpha, VEGF, and TNF-alpha levels in both chronic and aggressive form of periodontitis might suggest the role of TNF-alpha/HIF-1 alpha/VEGF pathway in the pathogenesis of periodontal diseases.