Filiz Bakar

Gold nanoparticle-lignan complexes inhibited MCF-7 cell proliferation in vitro: a novel conjugation for cancer therapy.

Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment and as therapeutic agents and drug delivery vehicles. Particularly lignans, also called phytoestrogens, have strong effects on the treatment of carcinomas due to their antiestrogenic, antiangiogenic and proapoptotic mechanism. The aim of this study is to investigate the antiproliferative effects of three lignans-AuNP conjugates, pinoresinol (PINO), lariciresinol (LARI) and secoisolariciresinol (SECO), on the MCF-7 cell lines. For this purpose, first, thiolated β-cyclodextrin (β-CD) was synthesized to achieve a surface modification of AuNP, and then the β-CD modified AuNP was characterized using the transmission electron microscopy (TEM), UV-Visible and Nuclear Magnetic Resonance (NMR) spectroscopy. Then, the selected lignans were conjugated to the β-CD-modified AuNP, and the antiproliferative effect of these conjugates was monitored. The results suggest that when compared to their non-conjugated forms, the AuNP-bound lignan conjugates prevented the proliferation of the MCF-7 cells significantly. Therefore, these AuNP-conjugated derivatives can be new candidate agents for breast cancer therapy.

Annexin V expression and anti-annexin V antibodies in type 1 diabetes.

BACKGROUND Annexin V (AnxV) has potent anticoagulant properties and regulatory functions for apoptosis and inflammation. Antibodies against annexin V (anti-AnxVs) may inhibit AnxV functions, leading to thrombosis during autoimmune diseases. Type 1 diabetes is an autoimmune disease and related with an ongoing autoimmune inflammation and thrombotic complications. There is no study evaluating anti-AnxVs/AnxV in a disease setting. OBJECTIVE The aim of this study was to evaluate the status of AnxV and anti-AnxVs in patients with type 1 diabetes. METHODS One hundred twenty-one patients with type 1 diabetes and 92 healthy controls were included in this study. Serum levels of AnxV and anti-AnxVs and expression of the AnxV gene and its common polymorphism in Kozak sequence (-1C>T) were studied. As a functional assay, the binding capacity of AnxV to platelets was evaluated. RESULTS As compared with controls, type 1 diabetic patients had significantly low serum AnxV levels and AnxV gene expression. The number of anti-AnxV positivity and their serum levels were significantly higher in type 1 diabetic patients than controls. AnxV binding to platelets were significantly decreased in the type 1 diabetic patients. The frequencies of the -1C>T polymorphism of AnxV gene did not differ between groups. CONCLUSIONS This study demonstrated the significant changes in AnxV levels and its function in type 1 diabetic patients. These results support the hypothesis that the defective AnxV system may have a role in ongoing autoimmune activity and the development of thrombotic complications in type 1 diabetes. Further studies are necessary to elucidate the clinical impact of anti-AnxVs and dysregulated AnxV function in type 1 diabetes.

Synthesis and potent cytotoxicity of some novel imidazopyridine derivatives against MCF-7 human breast adenocarcinoma cell line

A series of novel 2-phenyl-3H-imidazo[4,5-b]pyridines and 2-phenyl-3H-imidazo[4,5-c]pyridines and their precursors were synthesized. Their in vitro cytotoxicity against MCF-7 human breast adenocarcinoma cell line has been investigated, and some of the tested compounds have shown high cytotoxic activity against MCF-7 cells. N-Hydroxy-4-(3H-imidazo[4,5-b]pyridin-2-yl)benzenecarboximidamide was the most active compound with IC50 equal to 0.082 μM, which is an activity almost as high as that of a commonly used anticancer drugs docetaxel and imatinib mesylate.

Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus.

Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus.

Synthesis of new indole-2-carboxamide and 3-acetamide derivatives and evaluation their antioxidant properties.

In recent years, antioxidant compounds play an important role as a health-protecting factor. Antioxidants protect cells against the damaging effects of reactive oxygen species (ROS). An imbalance between antioxidants and ROS results in oxidative stress, which leads to cellular damage and it is linked to many vital diseases. It was shown that heme oxygenase (HO) provides efficient cytoprotection against oxidative stress. In this study, a series of indole-2-carboxamide and 3-acetamide derivatives was tested for in vitro effects on HO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. Among the synthesized compounds, N-[3-(dimethylamino)propyl]-1H-indole-2-carboxamide 3 was found as the most activator of HO and N-(2-(dimethylamino)ethyl)-2-(1H-indol-3-yl)acetamide 8 was found the most potent inhibitor for DPPH at 10−4 M concentration.

Neopterin and hsCRP are not correlated in gestational diabetes mellitus

Abstract Objective: To determine serum neopterin and high sensitive C-reactive protein (hsCRP) levels in patients with and without gestational diabetes mellitus (GDM). Methods: Neopterin and hsCRP levels were quantified in 28 women with GDM and 20 pregnant women with normal glucose tolerance (NGT). Postpartum neopterin and hsCRP levels were measured in a follow-up study. Results: Neopterin levels were significantly higher in women with GDM than in women with NGT (15.89 ± 8.19 nmol/L versus 10.4 ± 3.8 nmol/L, p < 0.008, respectively), however the levels significantly decreased after delivery in GDM group (15.89 ± 8.19 nmol/L versus 11.63 ± 5.96 nmol/L, p < 0.001). hsCRP levels were not different between women with and without GDM (5.74 ± 3.91 versus 5.73 ± 3.34, p = 0.9, respectively). In contrast, hsCRP levels decreased after delivery in patients with GDM (5.74 ± 3.91 versus 3.78 ± 2.78, p < 0.01). Neopterin levels were correlated with maternal age (r = 0.3, p = 0.02) and fasting glucose (r = 0.4, p = 0.004), postprandial glucose (r = 0.3, p = 0.01), HbA1c (r = 0.3, p = 0.02), whereas hsCRP levels were correlated with pre-pregnancy (r = 0.3, p = 0.04) and pregnancy body mass index (r = 0.4, p = 0.008). No correlation between serum neopterin and hsCRP levels was found (p = 0.9). Conclusion: Neopterin levels increased in patients with GDM; hence, it may be related to inflammation. However, the lack of correlation between neopterin and hsCRP suggests the role of different attitudes of these two parameters in the course of pregnancy and GDM.

The Effects of 1,3,5-trisubstituted Indole Derivatives on Cell Growth, Apoptosis and MMP-2/9 mRNA Expression of MCF-7 Human Breast Cancer Cells

BACKGROUND Matrix metalloproteinases are known as extracellular matrix degrading enzymes and have important role on tumor progression. OBJECTIVE This study reports the effects of 1,3,5-trisubstituted indole derivatives on cytotoxicity, apoptosis and MMP- 2/MMP-9 mRNA expression of MCF-7 human breast carcinoma cells. METHOD The cytotoxic effects of the compounds on MCF-7 cells were performed by MTT test, and cell proliferation was determined via BrdU incorporation. The apoptotic effects were observed by cell death detection elisa. The effects of the compounds on MMP-2/-9 enzyme activity and mRNA expression were also performed. RESULTS The compounds inhibited the proliferation of MCF-7 breast carcinoma cells significantly in a dose dependent manner. All compounds were able to induce DNA fragmentation, especially compound 1. The IC50 values of compound 2 and 4 for MMP-2 were 0.42 μM and 1.88 μM, respectively. MMP-2 mRNA expression results were correlated with the inhibition of enzyme activity, such compound 4 inhibited MMP-2 mRNA expression at all treated concentrations. Docking simulation has also been performed to analyze the binding mode of compounds and the results showed that compound 2, the most active compound, formed a hydrogen bond with Glu202 for binding to the MMP-2 active site. In addition, the hydrophobic parts of compound 2 are in contact with nonpolar surface areas of MMP-2, such as His201, His211, Tyr223 and Tyr193. CONCLUSION According to the molecular docking results along with the biological assay data, it is suggested that compound 2 might be used for further design and development of MMP-2 inhibitors.

Cucurbitacin B Enhances the Anticancer Effect of Imatinib Mesylate Through Inhibition of MMP-2 Expression in MCF-7 and SW480 Tumor Cell Lines.

The combination of medicinal plant extracts with known chemotherapeutics offers significant potential for the development of novel therapies in cancer disease. Cucurbitacin B (CuB) is one of the most potent and widely used members of cucurbitacin family and it is known to have important effects on several diseases including cancer. To determine whether CuB can enhance chemosensitivity to imatinib mesylate (IM), in the present study, the combined effects of CuB with IM on MCF-7 and SW480 cells were investigated. The cells were treated with CuB alone or in combination with IM and the results showed that the combination treatment synergistically inhibited cell proliferation and induced apoptosis. Furthermore, the combined effect of CuB and IM on matrix metalloproteinase-2 (MMP-2) gene expression, a member of MMP family which is responsible for the degradation of extracellular matrix was also evaluated. CuB increased the inhibitory effect of IM on MMP-2 expression synergistically in a dose dependent manner. The results suggest that CuB in combination with IM may serve as a potentially useful therapeutic strategy for patients with breast and colorectal cancer.

Antiproliferative activity of synthesized some new benzimidazole carboxamidines against MCF-7 breast carcinoma cells

Abstract Breast cancer is the most endemic cause of cancer among women in both developed and developing countries. Benzimidazole derivatives exemplify one of the chemical classes that show strong cytotoxic activity especially against breast cancer cells (MCF-7). Aromatic amidine derivatives are known as a group of DNA interactive compounds that bind minor groove of the genome, especially A-T base pairs, and show significant in vitro and in vivo toxicity toward cancer cells. In light of these studies, some new mono/dicationic amidino benzimidazole derivatives were synthesized and evaluated for cytotoxic activity on cultured MCF-7 breast cancer cells. Some of these compounds have strongly inhibited MCF-7 cell viability in a dose-dependent manner compared with clinically used reference compounds, imatinib mesylate and docetaxel. Among them, 4-[(5(6)-bromo-1H-benzimidazole-2-yl)amino]benzene-1-carboxamidine (30) showed the best inhibitory activity with IC50 value of 4.6 nM.

Evaluation of Antioxidant Activities and Phenolic Compounds of Scorzonera latifolia (Fisch. & Mey.) DC. Collected from Different Geographic Origins in Turkey

Objectives: The chemical composition of plants is considered to be affected by many parameters. Therefore, the region where the samples are collected is likely to have an influence on the composition of phenolic compounds, so that their biological activities. In the present study, evaluation of antioxidant activity potentials of Scorzonera latifolia (Fisch. & Mey.) DC. aerial parts and roots, which were collected from different regions of Turkey, was aimed. Materials and Methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and measurement of malondialdehyde (MDA) levels were used for determining antioxidant capacities of the tested extracts. In order to observe variations in the chemical composition of the investigated samples qualitatively as well as quantitatively, high performance liquid chromatography analyses were performed. Results: Quantitative analysis showed that the amounts of chlorogenic acid and hyperoside in plants vary according to the regions where the samples were collected. As a result aerial parts of the S. latifolia collected from the Kars region have found to contain higher amount of chlorogenic acid (1246.78±3.20 µg/g) as well as hyperoside (652.32±2.48 µg/g) than other samples. The highest DPPH radical scavenging activity was determined with the IC50 value of 1.036 mg/mL for S. latifolia aerial parts of Kayseri sample. MDA level was detected as the lowest with treatment of S. latifolia Bayburt root sample (4.41 nmol/mL). Conclusion: According to the antioxidant activity results, no significant difference was observed in the antioxidant potential between the samples collected from different locations except for S. latifolia collected from the Kars region.