Browsing by Author "Kiran B."

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Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells
(2015-06-29) Birsu Cincin Z.; Unlu M.; Kiran B.; Sinem Bireller E.; Baran Y.; Cakmakoglu B.
Purpose: Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. Methods: The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). Results: We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-κB signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. Conclusions: Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.
Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line
(2015-04-28) Cincin Z.; Unlu M.; Kiran B.; Bireller E.; Baran Y.; Cakmakoglu B.
Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of quercitrin. Although different studies indicated that quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines. Time and dose dependent antiproliferative and apoptotic effects of quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.
Assessment of Association Between the Potential Immunomodulatory Activity and Drinking Olive Leaf Tea in the Coronavirus Disease-2019 Pandemic: An Observational Study
(2022-12-01) Kocyigit A.; Guler E.M.; Irban A.; Kiran B.; Atayoglu A.T.
Objective: During the Coronavirus Disease-2019 (COVID-19) pandemic, in addition to the current measures, the healthy immune system plays an essential role and various natural agents have been recommended to boost innate immunity. The aim of this study was to investigate any association between the potential immunomodulatory activity and drinking olive leaf tea (OLT) in the COVID-19 pandemic. Design: The study was conducted among the workers in a tractor factory where OLT was served in routine. Drinking at least one cup of OLT per day for a minimum of 1 month was the inclusion criteria used in the study. The workers who had a history of vaccination and COVID-19 were excluded from the study, and lymphocyte subsets, interleukin (IL)-2, IFN-γ, COVID-19-specific IgM and IgG levels were analyzed in all the participants to determine the asymptomatic individuals among the participants and compare the immunological parameters. Results: The study was conducted among 336 workers, 183 of them were OLT drinkers and 153 were OLT nondrinkers. The results showed higher values of CD3-/CD16/56 (natural killer [NK]) cells, CD3+/CD16/56 (natural killer T [NKT]) cells, total NK (NK+NKT) cells, and serum IFN-γ, and IL-2 levels in OLT drinkers compared to the nondrinkers. Although all the OLT drinkers and nondrinkers included in the study reported no history of COVID-19, specific COVID-19 IgG levels were found positive in 60% of OLT drinkers and 38% OLT nondrinkers. Conclusions: Peripheral NK and NKT cell values and IL-2 and IFN-γsecretion levels were found higher in the OLT drinking group. There were positive correlations between the OLT drinking frequency and NK cell counts. Moreover, the number of individuals who had "asymptomatic"COVID-19 infection was higher in the OLT drinking group than in the nondrinking cohort.
Hesperidin promotes programmed cell death by downregulation of nongenomic estrogen receptor signalling pathway in endometrial cancer cells
(2018-07-01) Cincin Z.B.; Kiran B.; Baran Y.; Cakmakoglu B.
Endometrial carcinoma (EC) is the most common malignant gynecologic tumor in women. EC is thought to be caused by increasing estrogen levels relative to progesterone in the body. Hesperidin (Hsd), a biologically active flavonoid, could be extracted from Citrus species. It has been recently shown that Hsd could exert anticarcinogenic properties in different cancer types. However, the effects of Hsd and its molecular mechanisms on EC remain unclear. In this study, the antiproliferative, apoptotic and genomic effects of Hsd in EC and its underlying mechanisms were identified. We found that Hsd significantly suppressed the proliferation of EC cells in dose and time dependent manner. Mechanistic studies showed that Hsd could contribute apoptosis by inducing externalization of phosphatidyl serine (PS), caspase-3 activity and loss of mitochondrial membrane (MMP). Furthermore, we examined that Hsd could also significantly upregulate the expression of proapoptotic Bax subgroup genes (Bax and Bik) while downregulating the anti-apoptotic protein Bcl-2 in EC cell lines. According to GO enrichment and KEGG pathway analysis of differentially expressed genes in Hsd treated EC cells, we identified that Hsd could promote cell death via downregulation of estrogen receptor I (ESRI) that was directly related to ERK/MAPK pathway. Taken together, our study first showed that Hsd could be an antiestrogenic compound that could modulate nongenomic estrogen receptor signaling through inhibition of EC cell growth. Our findings may provide us a novel growth inhibitory agent for EC treatment after verifying its molecular mechanism with in vivo studies.
Individual and combined effects of CTLA4-CD28 variants and oxidant-antioxidant status on the development of colorectal cancer
(2015-10-01) Kucukhuseyin O.; Turan S.; Yanar K.; Arikan S.; Duzkoylu Y.; Aydin S.; Cakatay U.; Mezani B.; Farooqi A.A.; Aydinoʇlu Isitmangil G.; Kiran B.; Cacina C.; Nurdan Yenilmez E.; Ergen A.; Zeybek U.; Yaylim I.
Background: Colorectal cancer (CRC) is the third most frequent cancer worldwide. Research has revealed the contributions of the immune system and anti-inflammatory pathways in the development of cancer. The balance between cluster of differentiation 28 (CD28) and cytotoxic Tlymphocyte- associated protein 4 (CTLA4) signaling is important for the regulation of immune responses. The oxidant-antioxidant balance by sustaining redox control via several defense mechanisms is also an important factor for the progression of cancer. The aim of the present study was to determine the distribution of CTLA4/CD28 variants and oxidant-antioxidant status in patients with CRC. Materials and Methods: This study enrolled 80 patients with CRC and 115 healthy controls. We used a spectrophotometric assay to detect the levels of lipid peroxidation products malon dialdehyde (MDA) and lipid hydroperoxide (LHP), and measured the concentration of protein damage products, advanced oxidation protein products (AOPP) and protein carbonyl (PCO). Additionally, antioxidant levels were detected by measuring copper, zinc, superoxide dismutase (Zn-Cu SOD) and total thiol (T-SH) levels, and advanced glycation end-products (AGEs). The CTLA4 -318C>T, CTLA4 49A>G and CD28C>T genotypes were determined by using restriction enzymes. Results: AOPP and PCO levels were increased in patients with CRC as well as those of LHP, MDA and AGE, while the levels of antioxidants such as Cu-Zn SOD and T-SH were lower. Lower serum levels of CTLA4 and higher serum levels of CD28 were detected in patients and, an association of the CTLA4 -318C/T polymorphism was found in patients with CRC. Conclusion: Our oxidative stress was increased in patients with CRC, suggesting the contribution of this disturbed oxidative status to serum CTLA4 and CD28 levels, and to the pathogenesis of CRC.
K⁺ Channels and Some Familiar Antiepileptic Drugs: Evaluation of Their the Structure-Activity Relationships with Molecular Docking Analysis
(2023-05-31) Çakmak E.N.; Gür M.; Kiran B.
This study includes the structure-activity relationship of active molecules that are commonly used in the treatment of convulsive seizures in epileptic diseases. Well-known epileptic active molecules studied are: Vigabatrin, Lokosamidine, Zonisamide, Oxcarbazepine, Levetiresetam, Tiagabine, Topiramate, Lamotrigin, Gabapentin, Felbamat, Ethosuximide, Valproic Acid, Mesuximide, Ethotoin, Primidon, Trimethadion, Phenytoin, Remasemide, Mephenytoin. These molecules, which were selected considering the physiopathological mechanisms of action of epileptic disease, were considered suitable for molecular docking studies since they were used as a potential antiepileptic agent. In addition, it was focused on the potassium channels, which were prominent in the mechanisms of epilepsy. During the action potential that triggers seizure formation, inward rectifying potassium channels (KIR3.2) make a important role providing the flow of K+ ions. Thus, PDB ID: 4KFM receptor was chosen for molecular docking study, since its act as an agonist according to its activity on the canal in the case of epileptic seizures formation. The result of molecular docking analysis demonstrated that Phenytoin gave the best binding affinity for 4KFM with a value of-6.2 kcal/mol. Other analysis in descending order (as kcal/mol); Oxcarbazepine (-6,0), Remasemide (-5.9), Topiramate and Primidon (-5.8), Tiagabine, Felbamat and Mesuximide (-5.7), Lamotrigin (-5.6) Zonisamide, Ethotoin and Mephenytoin, Lokosamidine (-5.5), Gabapentin (-4.8), Trimethadion (-4.7), Ethosuximide (-4.6), Levetiresetam (-4.5), Vigabatrin (-4.0), Valproic Acid (-3.9) determined as.
Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer
(2014-08-01) Cincin Z.B.; Unlu M.; Kiran B.; Bireller E.S.; Baran Y.; Cakmakoglu B.
Background and Aims: Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of quercitrin and the molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines. Methods: Time- and dose-dependent antiproliferative and apoptotic effects of quercitrin determined by WST-1cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. Results: There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner. Conclusion: Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549cells. These results revealed that quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects invivo, quercitrin could be a novel and strong anticancer agent against NSCLC.
Regulatory T cells in kidney transplant recipients with LIMS1 rs893403 risk genotype
(2024-04-01) Mirioglu S.; Kiran B.; Lentine K.L.; Edwards J.C.; Caliskan Y.
The Role of Activated Cytotoxic T Cells in Etiopathogenesis of Periodontal Disease: Does It Harm or Does It Heal?
(2015-03-19) Cifcibasi E.; Ciblak M.; Kiran B.; Badur S.; Firatli E.; Issever H.; Cintan S.
The objective of this study was to determine the phenotypic profile of blood mononuclear cells, specifically CD8+/CD28+ cells, in patients with generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) in peripheral blood and in blood obtained from periodontal defect site which might contribute to tissue damage. 13 GAgP, 11 chronic periodontitis (CP) and 5 healthy controls (H) were included in the study. Plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD) and clinical attachment level (CAL) were recorded. Blood from the base of periodontal defect site and peripheral blood from the antecubital vein were obtained. Relative counts of CD45+, CD3+, CD4+, CD8+/CD28+, CD8+/CD28-, CD19+, CD16+/CD56+/CD3, CD3+/CD16+/CD56+ receptors were determined with two color flow cytometry using monoclonal antibodies. BoP, PPD and CAL were significantly higher in both periodontitis groups than healthy controls (p <0.05). Activated cytotoxic T cells, CD8+/CD28+ cells, were significantly elevated in GAgP and CP groups compared to HC both in blood obtained from defect site and blood obtained from systemic circulation (p <0.05). GAgP and CP patients have an increased levels of activated cytotoxic T cells as a result of inflammation which may cause severe tissue damage that lead to severe and rapid loss of periodontal tissues.