Tugce Balci

Genistein-induced mir-23b expression inhibits the growth of breast cancer cells

Aim of the study Genistein, an isoflavonoid, plays roles in the inhibition of protein tyrosine kinase phosphorylation, induction of apoptosis, and cell differentiation in breast cancer. This study aims to induce cellular stress by exposing genistein to determine alterations of miRNA expression profiles in MCF-7 cells. Material and methods XTT assay and trypan blue dye exclusion assays were performed to examine the cytotoxic effects of genistein treatment. Expressions of miRNAs were quantified using Real-Time Online RT-PCR. Results The IC50 dose of genistein was 175 μM in MCF-7 cell, line and the cytotoxic effect of genistein was detected after 48 hours. miR-23b was found to be up-regulated 56.69 fold following the treatment of genistein. It was found that miR-23b was upregulated for MCF-7 breast cancer cells after genistein treatment. Conclusions Up-regulated ex-expression of miR-23b might be a putative biomarker for use in the therapy of breast cancer patients. miR-23b up-regulation might be important in terms of response to genistein.

Design of polyethylene glycol-polyethylenimine nanocomplexes as non-viral carriers: mir-150 delivery to chronic myeloid leukemia cells

MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many biological processes, and they have been pioneered as therapeutic targets for curing disease. miRNAs are single‐stranded, small (19–22 nt) regulatory non‐coding RNAs whose deregulation of expression triggers human cancers, including leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs can function as tumour suppressors (suppressing malignant potential) or oncogenes (activating malignant potential) like actors of complex diseases. To address the issue of overcoming instability and low transfection efficiency in vitro, the polyethylene glycol–polyethyleneimine (PEG–PEI) nanoparticle was used as non‐viral vector carrier for miR‐150 transfection, which is downregulated in chronic myeloid leukemia. PEG–PEI [PEG(550)3‐g‐PEI(1800)]/miRNA nanocomplexes were synthesised and characterised by particle size distribution (PSD), polydispersity index (PDI) and zeta potential, surface charge, their cytotoxicity, and transfection efficiency. Interaction with human leukemia cells (K‐562 and KU812) and control cells NCI‐BL2347 with them has been investigated. The transfection efficiency of PEG–PEI/miRNA at N/P 26 rose 6.7‐fold above the control by qRT‐PCR. The size of homogenous nanocomplexes (PBI < 0.5) was 160.8 ± 11 nm. The data indicate that PEG–PEI may be an encouraging non‐viral carrier for altering miRNA expression in the treatment of chronic myeloid leukemia, with many advantages such as relatively high miRNA transfection efficiency and low cytotoxicity.

Analysis of dysregulated long non-coding RNA expressions in glioblastoma cells.

Long non coding RNAs (lncRNAs) are associated with various biological roles such as embryogenesis, stem cell biology, cellular development and present specific tissue expression profiles. Aberrant expression of lncRNAs are thought to play a critical role in the progression and development of various cancer types, including gliomas. Glioblastomas (GBM) are common and malignant primary brain tumours. Brain cancer stem cells (BCSC) are isolated from both low and high-grade tumours in adults and children, by cell fraction which express neuronal stem cell surface marker CD133. The purpose of this study was to investigate the expression profiles of lncRNAs in brain tumour cells and determine its potential biological function. For this purpose, U118MG-U87MG; GBM stem cell series were used. Human parental brain cancer cells were included as the control group; the expressions of disease related human lncRNA profiles were studied by LightCycler 480 real-time PCR. Expression profiles of 83 lncRNA genes were analyzed for a significant dysregulation, compared to the control cells. Among lncRNAs, 51 lncRNA genes down-regulated, while 8 lncRNA genes were up-regulated. PCAT-1 (-2.36), MEG3 (-5.34), HOTAIR (-2.48) lncRNAs showed low expression in glioblastoma compared to the human (parental) brain cancer stem cells, indicating their role as tumour suppressor genes on gliomas. As a result, significant changes for anti-cancer gene expressions were detected with disease-related human lncRNA array plates. Identification of novel target genes may lead to promising developments in human brain cancer treatment.

In vitro evaluation of apoptosis with 99mTc-glucoheptonate

Radiopharmaceuticals are useful to evaluate effectiveness of cancer treatments as well as diagnosis of diseases. (99m)Tc-Glucoheptonate has high sensitivity for imaging lung cancer tissues. In this study, the potential use of (99m)Tc-glucoheptonate for monitoring apoptosis related to chemotherapeutic agents is investigated in vitro using A549 lung cancer cell line. A decrease in (99m)Tc-glucoheptonate uptake ratio was observed depending on the level of apoptosis. (99m)Tc-glucoheptonate is found to be useful for the detection of apoptosis following treatment in A549 lung tumor cells.

The effect of tomatine on metastasis related matrix metalloproteinase (MMP) activities in breast cancer cell model

Breast cancer is one of the most common malignancies in women and metastasis is the cause of morbidity and mortality in patients. In the development of metastasis, the matrix metalloproteinase (MMP) family has a very important role in tumor development. MMP-2 and MMP-9 work together for extracellular matrix (ECM) cleavage to increase migration. Tomatine is a secondary metabolite that has a natural defense role against plants, fungi, viruses and bacteria that are synthesized from tomato. In additıon, tomatine is also known that it breaks down the cell membrane and is a strong inhibitor in human cancer cells. In this study, it was aimed to evaluate the effect of tomatine on cytotoxicity, apoptosis and matrix metalloproteinase inhibition in MCF-7 cell lines. Human breast cancer cell line (MCF-7) was used as a cell line. In MCF-7 cells, the IC50 dose of tomatine was determined to be 7.07μM. According to the control cells, apoptosis increased 3.4 fold in 48thh. Activation of MMP-2, MMP-9 and MMP-9\NGAL has been shown to decrease significantly in cells treated with tomatine by gelatin zymography compared to the control. As a result, matrix metalloproteinase activity and cell proliferation were suppressed by tomatine and this may provide support in treatment methods.

Meta-analysis of the relationship between MnSOD polymorphism and cancer in the Turkish and Cypriot population

Abstract Objectives: The association between manganese superoxide dismutase (MnSOD) p.Val16Ala polymorphism and cancer has been shown in various studies. The aim of this study is to investigate the relationship between MnSOD polymorphism (V/V, V/A, A/A) and cancer in the Turkish and Cypriot population through meta-analysis. Material and methods: The present study included meta-analysis of 14 publications covering 2413 cancer patients and 2907 healthy control groups from 2005 to 2016. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the random effect model of DerSimonian and Laird for each study. Publication bias was checked with funnel plot by Begg’s and Egger’s test statistics. Results: Meta-analysis of MnSOD polymorphism was performed in the additive model (AV vs. VV; OR=1.133, 95% CI: 1.002–1.282), allele contrast (A vs. V; OR=1.016, 95% CI: 0.930–1.278), homozygote model (AA vs. VV; OR=0.983, 95% CI: 0.839–1.153), dominant model (AA+AV vs. VV; OR=1.090, 95% CI: 0.971–1.223) and recessive model (AA vs. AV+VV; OR=0.924, 95% CI: 0.803–1.064). The A/V genotype polymorphism was found be significant for cancer. Conclusion: The frequency of the A/V heterozygote genotype of the MnSOD polymorphisms is found to be higher in the Cypriot and Turkish populations than any other genotype.