Browsing by Author "Karatas, Omer Faruk"

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Alpha-B Expression in Human Laryngeal Squamous Cell Carcinoma Tissues
(Wiley, 2015) Yilmaz, Mehmet; Karatas, Omer Faruk; Yuceturk, Betul; Dag, Huseyin; Yener, Murat; Ozen, Mustafa
BackgroundLaryngeal squamous cell carcinoma (SCC), being an aggressive malignancy, is one of the most commonly diagnosed malignant types of head and neck SCC worldwide. The recent studies suggested that B-crystallin might play an important role in tumorigenesis. The purpose of this study was to investigate the B-crystallin expression level in metastatic and nonmetastatic laryngeal SCC tissues and to determine its prognostic significance. MethodsAlpha-B-crystallin expression status in metastatic, nonmetastatic laryngeal SCC, and normal tissue samples was investigated by quantitative real-time polymerase chain reaction (qRT-PCR). ResultsWe demonstrated that the expression of B-crystallin was significantly upregulated in laryngeal SCC tumor tissue samples in comparison with the corresponding normal tissues (p<.001), although no significant association has been found between B-crystallin expression and either the metastatic potential or the T classification of the specimens. ConclusionAlthough expression of B-crystallin is not statistically correlated with neck metastases, we demonstrated that B-crystallin is significantly overexpressed in laryngeal cancer. (c) 2014 Wiley Periodicals, Inc. Head Neck 37: 1344-1348, 2015
The Altered Promoter Methylation of Oxytocin Receptor Gene in Autism
(Taylor & Francis Ltd, 2016) Yuksel, Mine Elagoz; Yuceturk, Betul; Karatas, Omer Faruk; Ozen, Mustafa; Dogangung, Burak
Autism spectrum disorder (ASD) is one of the lifelong existing disorders. Abnormal methylation status of gene promoters of oxytonergic system has been implicated as among the etiologic factors of ASDs. We, therefore, investigated the methylation frequency of oxytocin receptor gene (OXTR) promoter from peripheral blood samples of children with autistic features. Our sample includes 66 children in total (22-94 months); 27 children with ASDs according to the DSM-IV-TR and the Childhood Autism Rating Scale (CARS) and 39 children who do not have any autistic like symptoms as the healthy control group. We investigated the DNA methylation status of OXTR promoter by methylation specific enzymatic digestion of genomic DNA and polymerase chain reaction. A significant relationship has been found between ASDs and healthy controls for the reduction of methylation frequency of the regions MT1 and MT3 of OXTR. We could not find any association in the methylation frequency of MT2 and MT4 regions of OXTR. Although our findings indicate high frequency of OXTR promoter hypomethylation in ASDs, there is need for independent replication of the results for a bigger sample set. We expect that future studies with the inclusion of larger, more homogeneous samples will attempt to disentangle the causes of ASDs.
Antiproliferative Potential of miR33a in Laryngeal Cancer Hep-2 Cells Via Targeting Pim1
(Wiley, 2018) Karatas, Omer Faruk
Background Laryngeal cancer is a frequent cause of cancer-associated mortality worldwide with an overall poor prognosis along with high mortality rates. Therefore, comprehensive investigation of underlying molecular mechanisms of laryngeal carcinogenesis remains an important problem. Methods In this study, proliferative and apoptotic features of Hep-2 cells overexpressing microRNA-33a (miR-33a) were evaluated and in silico analysis along with literature search was used to find putative targets of miR-33a. The potential of PIM1 (pim-1 oncogene) as a direct target of miR-33a was tested using quantitative real-time polymerase chain reaction, Western blot, and luciferase assay. Results Induced miR-33a expression significantly inhibited proliferation through inducing apoptosis of Hep-2 cells. Further in vitro tests showed downregulation of PIM1 in messenger ribonucleic acid (mRNA) and protein level upon miR-33a overexpression and confirmed PIM1 as a direct target of miR-33a. Conclusions Mir-33a was demonstrated to act as a tumor suppressor in larnygeal cancer via directly targeting the 3 ' untranslated region of PIM1.
Azd4547 Targets the Fgfr/Akt Axis to Overcome Paclitaxel Resistance in Head and Neck Cancer
(Springer, 2022) Aytatli, Abdulmelik; Barlak, Neslisah; Sanli, Fatma; Caglar, Hasan Onur; Gundogdu, Betul; Tatar, Arzu; Karatas, Omer Faruk
Purpose Development of chemoresistance is one of the major obstacles to the treatment of head and neck squamous cell carcinoma (HNSCC). The PI3K/Akt pathway, involved in drug resistance, has been found to be overactivated in > 90% of HNSCCs. Aberrant activation of the FGF receptors (FGFRs) has been reported to cause overactivation of the PI3K/Akt pathway and to be associated with the maintenance of stem cell features, which is controlled via SOX2 expression. In this study, we aimed at investigating the potential of using AZD4547, an orally bioavailable FGFR inhibitor, to overcome taxol-resistance by targeting the FGFR/Akt/SOX2 axis in HNSCC. Methods We initially evaluated FGFR2 and SOX2 expression using in silico tools. We analyzed the FGFR/Akt/SOX2 axis in normal/tumor tissue pairs and in recombinant FGF2 treated HNSCC cells. Next, we explored the effects of AZD4547 alone and in combination with taxol on the proliferation, migration and colony forming capacities of parental/taxol-resistant cells using in vitro models. Results We found that the p-FGFR, p-AKT, p-GSK-3 beta and SOX2 expression levels were higher in tumor tissues than in its corresponding normal tissues, and that AZD4547 effectively suppressed the expression of FGFR and its downstream targets in recombinant FGF2 treated HNSCC cells. We also found that AZD4547 diminished the viability, migration and colony forming capacity of HNSCC cells, and that co-treatment with taxol potentiated the impact of taxol on these cells. Finally, we found that AZD4547 inhibited the overexpressed FGFR/Akt/SOX2 axis and profoundly suppressed cancer-related phenotypes in taxol-resistant HNSCC cells. Conclusion From our data we conclude that AZD4547 may increase the impact of taxol during HNSCC treatment. We suggest AZD4547 as a therapeutic agent to overcome taxol-resistance.
A Biochemistry-Oriented Drug Design: Synthesis, Anticancer Activity, Enzymes Inhibition, Molecular Docking Studies of Novel 1,2,4-Triazole Derivatives
(Taylor & Francis Inc, 2024) Yuriy, Karpenko; Kusdemir, Gulnur; Volodymyr, Parchenko; Tuzun, Burak; Taslimi, Parham; Karatas, Omer Faruk; Sayin, Koray
In this study, we researched the reactions of 5-(5-bromofuran-2-yl)-4-methyl-1,2,4-triazole-3-thiol and 5-thiophene-(3-ylmethyl)-4R-1,2,4-triazole-3-thiols with some halogen-containing compounds, a number of new compounds were synthesized (1.1-1.5 and 2.1-2.8). These compounds showed excellent to good inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. For obtaining the effects of these compounds on AChE and BChE enzymes were determined spectrophotometrically according to Ellman. IC50 values of these enzymes were ranging between 1.63 and 17.68 nM for AChE and 8.71 and 84.02 nM for BChE. After, prostate cancer is the second leading cause of cancer-related mortality for men over the age of 65 in developed countries. Current treatment options remain limited in the treatment of advanced-stage prostate cancer leading to biochemical recurrence in almost 40% of the patients. Therefore, there is an urgent need for development of novel therapeutic tools for treatment of prostate cancer patients. In this study, we aimed at analyzing the potential of all compounds against prostate cancer cells. We found that, of the tested compounds, 2.1, 2.2 and 2.3 showed significant cytotoxic activities against PC3 prostate cancer cells, although their effect on the viability of normal prostate cells was limited. These findings suggest their selective targeting potential for prostate cancer cells and offer them as candidate therapeutic agents against prostate cancer. The inhibitory activities of some chemical compounds, such as (1.1-1.5 and 2.1-2.8) were assessed by performing the molecular docking study in the presence of AChE, BChE and prostate cancer protein. MM/GBSA methods are calculated binding free energy. Finally, ADME/T analysis was performed to examine the drug properties of the 13 studied molecules.Communicated by Ramaswamy H. Sarma
Bioinformatics Approach Combined with Experimental Verification Reveals Oas3 Gene Implicated in Paclitaxel Resistance in Head and Neck Cancer
(Wiley, 2024) Caglar, Hasan Onur; Aytatli, Abdulmelik; Barlak, Neslisah; Karatas, Elanur Aydin; Tatar, Arzu; Sahin, Abdulkadir; Karatas, Omer Faruk
Background: This study aimed to identify a candidate gene associated with paclitaxel (PTX) resistance and to evaluate functionally its biological role in the PTX-resistant head and neck squamous cell carcinoma (HNSCC) cell lines and clinical specimens. Methods: Microarray data series containing samples of different types of cancers resistant to PTX were analyzed and then a candidate gene associated with PTX resistance was identified using various bioinformatics tools. After the suppression of the target gene expression, changes in cell viability and colony-forming ability were evaluated in PTX-resistant FaDu and SCC-9 cell lines. Results: Bioinformatics analyses of upregulated genes in PTX-resistant cancer cells indicated that OAS3 was associated with PTX resistance. The downregulation of OAS3 expression significantly reduced the viability and colony-forming capacity of PTX-resistant SCC-9 cells by inducing apoptosis and cell cycle arrest at G0/G1 phase. Conclusions: The therapeutic targeting of OAS3 may resensitize PTX-resistant HNSCC cells with high OAS3 expression to PTX treatment.
Bischalcone Derivatives with Fluorine and Methoxy Functional Groups: Synthesis, Molecular Docking, and Biological Evaluation as Potential Anticancer Agents
(Elsevier, 2025) Ozcan, Seyda; Anil, Derya Aktas; Ozkat, Gozde Yalcin; Sanli, Fatma; Karatas, Omer Faruk; Burmaoglu, Serdar
The present study employed the Claisen-Schmidt condensation reaction to synthesize a series of bischalcones featuring fluorine atoms positioned at different positions in the B rings and 1,3,5-trimethoxy groups in the A ring. The impact of these bischalcones on head and neck cancer cells was assessed through in vitro and in silico methodologies. As determined by the cell viability assay, compound 20, which had an IC50 value of 6.5 +/- 0.2 mu M, was the most lethal to FaDu cells of all compounds, although its cytotoxicity against healthy PNT1a cells was relatively low. Molecular docking and molecular dynamics simulations were performed on five receptors identified through in silico biological activity analysis: EGFR, Pim-1 kinase, PI3K alpha/mTOR, VEGFR, and P2Y1 Purinergic receptor. The compounds exhibited a primary target of EGFR, as evidenced by their effectiveness that was approximately one hundred times greater than that of the reference molecule. Compounds 18 and 20 exhibited remarkable efficacies as precursors to anticancer drugs.
CASC11 Promotes Aggressiveness of Prostate Cancer Cells Through miR145/Igf1r Axis
(Springer Nature, 2021) Capik, Ozel; Sanli, Fatma; Kurt, Ali; Ceylan, Onur; Suer, Ilknur; Kaya, Murat; Karatas, Omer Faruk
Background Prostate cancer (PCa) is the most common malignancy diagnosed among men after lung cancer in developed countries. Investigation of the underlying molecular mechanisms of PCa is urgently needed in order to develop better therapeutic strategies and to reveal more effective therapeutic targets. In this study, we aimed at exploring the potential functions of CASC11 in association with miR-145 and IGF1R during the malignant progression of PCa cells. Methods We initially investigated the oncogenic potential of noncoding members of CASC gene family and analyzed the effects of CASC11 overexpression on proliferation, migration, and colony formation ability of DU145, LNCaP, and PC3 PCa cells. We, then, exprlored the association of CASC11, miR-145, and IGF1R expression and their impacts on PI3K/AKT/mTOR signaling pathway in in vitro models. Results In silico analysis revealed that of the CASC family only CASC11 showed consistent results considering its differential expression as well as its association with the overall survival of patients. We demonstrated that ectopic overexpression of CASC11 significantly increased the proliferation, colony formation, and migration capacity in all three cell lines. CASC11 overexpression caused suppression of miR-145 and overexpression of IGF1R, leading to activation of PI3K/AKT/mTOR signaling pathway. Conclusion In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.
Cdr1as/miR7-5p Axis Contributes to the Suppression of Cell Viability in Prostate Cancer
(Walter de Gruyter Gmbh, 2025) Kaya, Murat; Suer, Ilknur; Aytatli, Abdulmelik; Karatas, Omer Faruk; Palanduz, Sukru; Cefle, Kivanc; Ozturk, Sukru
Background Prostate cancer is the most frequently diagnosed male cancer and the fifth highest cause of cancer mortality in men. CDR1as has played an essential role in the growth of several malignancies. However, its significance in the progression of prostate cancer has not been investigated. We aimed to investigate the role and mechanism of CDR1as in the development of prostate cancer and identify a new target for diagnostics and treatment.Methods CDR1as siRNA and miR-7-5p mimic were transfected into PC3 and DU145 PCa cell lines and their effects on cellular processes were investigated. Cell viability was measured by WST-8 assay. The role of CDR1as and/or miR-7-5p on PCa cell migration was detected using the scratch-wound assay. The apoptotic capacity of the cells was evaluated using the Caspase-3 kit. The potential targets of miR-7-5p were defined via in silico tools. mRNA and protein expression levels of IGF1R and EIF4E were detected by qRT-PCR and western blot assays, respectively. The matching between miR-7-5p and IGF1R was defined via luciferase reporter assay.Results Inhibiting CDR1as or restoring miR-7-5p reduced prostate cancer cell proliferation and migration while increasing apoptosis. Silencing CDR1as elevated the expression of miR-7-5p while decreasing IGF1R.Conclusions CDR1as functions as a miR-7-5p sponge, increasing IGF1R expression and promoting tumor development.
Characterization of Stem-Like Cells Directly Isolated from Freshly Resected Laryngeal Squamous Cell Carcinoma Specimens
(Bentham Science Publ Ltd, 2014) Suer, Ilknur; Karatas, Omer Faruk; Yuceturk, Betul; Yilmaz, Mehmet; Guven, Gulgun; Oz, Buge; Ozen, Mustafa
Larynx cancer (LCa) is an aggressive malignancy, which is the second most common malignant neoplasm of head and neck squamous cell carcinoma. Its incidences have been reported to increase and therapeutic options mostly fail to give positive clinical response especially for the advanced LCa cases. In this study we aimed to isolate stem-like cells from freshly resected LCa tumor specimens and characterize them by quantitative real time PCR (qRT-PCR) for expression of cancer stem cell markers including SOX2, OCT4, KLF4, ABCG2, CXCR4 and CD44. Our results showed that CD133(high) cells directly isolated from freshly resected tumor specimens exhibit elevated levels of SOX2, OCT4 and KLF4, and have increased expression levels of ABCG2 and CXCR4, which were associated with resistance of tumors to regular chemotherapeutic reagents. In conclusion, this study offers a useful approach utilizing CD133 to isolate stem cells directly from fresh tissues, which gives the opportunity to develop novel therapeutic tools specifically targeting these cells through their further characterization.
Characterization of Stem-Like Cells in a New Astroblastoma Cell Line
(Elsevier Inc, 2017) Coban, Esra Aydemir; Kasikci, Ezgi; Karatas, Omer Faruk; Suakar, Oznur; Kuskucu, Aysegul; Altunbek, Mine; Bayrak, Omer Faruk
Cell lines established from tumors are the most commonly used models in cancer research, and their use in recent years has enabled a greater understanding of the biology of cancer and the means to develop effective treatment strategies. Astroblastomas are uncommon neuroepithelial tumors of glial origin, predominantly affecting young people, mainly teenagers and children, predominantly females. To date, only a single study has reported that astroblastomas contain a large number of neural stem-like cells, which had only a partial proliferation capacity and differentiation. Our objective was to establish an astroblastoma cell line to investigate the presence of astroblastic cells and cancer stem-like cells. The migratory and invasion abilities of the cells were quantified with invasion and migration assays and compared to a glioblastoma cell line. The presence of stem cells was detected with surface-marker analysis by using flow cytometry, and measuring the differentiation ability with a differentiation assay and the self-renewal capacity with a sphere-forming assay. These characteristics may determine whether this novel cell line is a model for astroblastomas that may have stem cell characteristics. With this novel cell line, scientists can investigate the molecular pathways underlying astroblastomas and develop new therapeutic strategies for patients with these tumors.
Comprehensive in Silico Analysis for Identification of Novel Candidate Target Genes, Including DHX36, OPA1, and SENP2, Located on Chromosome 3q in Head and Neck Cancers
(Wiley, 2021) Karatas, Omer Faruk; Capik, Ozel; Barlak, Neslisah; Aydin Karatas, Elanur
Background Major milestones of head and neck carcinogenesis have been associated with various genetic abnormalities; however, a clear picture of the molecular networks deregulated during the carcinogenesis of head and neck squamous cell carcinoma (HNSC) has not yet completely revealed. Methods In this study, we usedin silicotools and online data sets to evaluate the underlying reasons for the expressional changes of genes residing within the chromosome 3q and to help understanding their contributions to HNSC carcinogenesis. Results We found that 13 of 20 most upregulated genes in HNSC are localized to 3q. Further analysis revealed a gene signature consisting ofDHX36,OPA1, andSENP2, which showed significant correlation in HNSC samples and potentially be deregulated through similar mechanisms including DNA amplification, transcriptional, and posttranscriptional regulation. Conclusions Considering our findings, we suggestDHX36,OPA1, andSENP2genes as overexpressed in HNSC tumors and that might be concurrently involved in HNSC carcinogenesis, tumor progression, and induction of angiogenic pathways.
Could the "Stiff Rim Sign" Be an Indicator of Lysyl Oxidase Activity in Breast Cancer
(Kowsar Publ, 2019) Kayadibi, Yasemin; Kilic, Fahrettin; Karatas, Omer Faruk; Ilvan, Sennur; Esmerer, Emel Ure; Kayadibi, Turgut; Yilmaz, Mehmet Halit
Background: Shear wave elastography (SWE) is a non-invasive and easily applicable imaging modality, which can provide quantitative information of tissue stiffness. Peritumoral high SWE elasticity values (stiff rim sign) has been reported in many studies. Lysyl oxidase (LOX) enzyme is implicated in the formation of peri-tumoral stiffness. Objectives: The aim of the study was to investigate the correlation between SWE measures with LOX gene expression levels in breast cancer patients. Patients and Methods: Forty seven women were included in the study. The lesions evaluated by SWE and ultrasound guided tru-cut biopsies were performed from both of the central and peripheral parts. SWE values, LOX family gene expression levels, histopathological features of the lesions, as well as axillary and distant metastasis statuses were evaluated statistically. Results: Thirty of the patients had breast cancer (BC) (the patient group) and17 of them had fibroadenoma (the control group). Lysyl oxidase lilcei (LOXL1) expression level in BC samples (central parts) were found to be significantly higher than the control group (P = 0.022). Stiff rim sign was present in all BC lesions and none of the control group. The elastography values of the patient group were significantly higher than the control group statistically (P 0.05) both for patient and control groups. Conclusion: Although there were no significant correlations between LOX expressions and SWE parameters in our study, axillary and distant metastasis were found to be correlated with SWE features, which emphasized the prognostic potential of SWE.
CXCL14 and miR4484 Serves as Potential Salivary Biomarkers for Early Detection of Peri-Implantitis
(Springer, 2024) Urvasizoglu, Gelengul; Kilic, Ahsen; Capik, Ozel; Gundogdu, Mustafa; Karatas, Omer Faruk
Peri-implantitis develops in 43.3% of implant patients, which affects tissues around the implant that may ultimately cause implant loss if not treated properly. Due to difficulties in detecting peri-implantitis in its early phases, implant failures are constantly on the rise. Therefore, new specific molecular markers need to be identified to prevent or limit disease progression in peri-implantitis patients. We investigated levels of CXCL9, CXCL12, and CXCL14 in saliva samples of 45 patients with commercially pure grade 4/5 Titanium-Aluminum-Vanadium implants. We analyzed the correlation of the chemokine levels using Pearson's Correlation test and investigated their power to discriminate peri-implantitis vs. non-peri-implantitis patients using receiver operating characteristic analysis. Our in silico investigation revealed CXCL9, CXCL12, and CXCL14 as predicted targets of miR-4484, which has been demonstrated as a powerful biomarker candidate for early detection of peri-implantitis in our previous study. We measured high CXCL9 and low CXCL14 levels in the saliva of peri-implantitis patients. We also reported that the CXCL14 level showed a significant positive correlation with miR-4484. Besides, CXCL14 together with miR-4484 in saliva differentiated peri-implantitis patients from non-peri-implantitis individuals with 100% success. We offer differential expressions of CXCL14 and miR-4484 in the saliva of patients with peri-implantitis as potential salivary biomarkers for early detection of this disease.
Design, Synthesis, and Biological Evaluation of Indole-Modified Tamoxifen Relatives as Potent Anticancer Agents
(Royal Society of Chemistry, 2023) Ertugrul, Berrak; Aytatli, Abdulmelik; Karatas, Omer Faruk; Saracoglu, Nurullah
Modulation of existing drugs is an attractive strategy to achieve improved activity in cancer therapy by lowering their effective dose. Preparation of relatives has been suggested and explored to improve the therapeutic effect of anticancer agents. In the current study, we attempted to modulate tamoxifen (TMX) by replacing the C-phenyl ring in its backbone with an indole or oxindole. In addition, it was possible to convert indole-modified tamoxifens to the corresponding 3,3'-bis(indolyl)methanes (BIMs) via an electrophilic substitution reaction with various benzaldehydes. We analyzed the anticancer potential of these indole-modified tamoxifens against various breast cancer cell lines and identified certain tamoxifen relatives with the potential to treat estrogen receptor (ER)-positive breast cancers, based on preliminary results of cell viability and caspase activity assays. The indole-modified tamoxifen BIM-Z,Z-35b, BIM-Z,Z-35f, and E-33 selectively reduced the viability of receptor-sensitive breast cancer cells more effectively than tamoxifen and suppressed the expression of ER-regulated genes. Moreover, Caspase-8 activity showed a specific increase in MCF-7 cells treated with these compounds. Our results indicate that these compounds may be an alternative to tamoxifen for the treatment of breast cancer.
Designing a Gold Nanoparticle-Based Nanocarrier for Microrna Transfection Into the Prostate and Breast Cancer Cells
(Wiley-Blackwell, 2014) Ekin, Asli; Karatas, Omer Faruk; Culha, Mustafa; Ozen, Mustafa
BackgroundCancer is one of the most common causes of human deaths worldwide. Nanotechnology has the potential to facilitate the detection, diagnosis, and treatment of cancer cases. Successful delivery of nucleic acids into cancer cells with the use of nanoparticles would be a significant improvement for medical and cellular biology. The use of nanoparticle-based vehicles in clinical treatment is considerably important for treating genetic disorders. Gold nanoparticles (AuNPs) have been suggested as therapeutic delivery tools for cancer. Because microRNAs (miRNAs), which induce post-transcriptional gene silencing, are deregulated in cancer cells, they are also considered as strong candidates for cancer therapy applications. In prostate and breast cancer, miR-145, a well-known tumor suppressor miRNA, is strongly downregulated in tumor tissues compared to their corresponding normal tissues. MethodsIn the present study, we aimed to use engineered AuNPs as nanocarrier platforms to deliver miRNAs to prostate/breast cancer cells. 13-nm AuNPs were modified with thiolated RNAs and then the miR-145 was hybridized to the RNAs that were chemically attached to the AuNPs. ResultsThe results obtained in the present study demonstrate the efficient delivery of miR-145 to prostate/breast cancer cells. We also show that delivery was more efficient when the AuNP-RNA-miRNA carrier complex was formed at an elevated temperature of 72 degrees C. ConclusionsIn conclusion, we show that AuNPs help the effective in vitro delivery of miR-145 into cancer cells. Copyright (c) 2014 John Wiley & Sons, Ltd.
Differential Expression of ABCB1, ABCG2, and KLF4 as Putative Indicators for Paclitaxel Resistance in Human Epithelial Type 2 Cells
(Springer, 2021) Duz, Mehmet Bugrahan; Karatas, Omer Faruk
Laryngeal squamous cell carcinoma (LSCC) is the second most common malignancy of the head and neck region in the USA with a declining 5-year survival rate. Paclitaxel resistance of tumors including LSCC still stands as a vital cause for poor clinical outcome in patients. In the current study, our aim was to explore the expressions of ATP-binding cassette transporters and stemness associated genes in human epithelial type 2 (Hep-2) cells with paclitaxel resistance. Resistant cells were developed via treatment with increasing doses of paclitaxel to acquire four sub-lines resistant to one-, two-, four-, and eightfold concentrations of paclitaxel (1x, 2x, 4x, 8x). Then, we profiled the expressions of ten selected ABC transporters (ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10, ABCF2, and ABCG2) and four stem cell markers (SOX2, OCT4, KLF, and CXCR4) using quantitative real time polymerase chain reaction in paclitaxel resistant cells to look for a link between these markers and chemoresistance. We demonstrated that ABCB1 and ABCG2 expressions gradually elevated and reached a maximum level in Taxol 8x cells. Considering stem cell markers, KLF4 expression elevated significantly, as soon as parental cells acquired resistance to the lowest dose of paclitaxel and its expression elevated stepwise. Expression levels of other tested ATP-binding cassette transporters and stem cell markers also elevated, although at different steps of paclitaxel resistance acquisition. Our findings suggest that higher expressions of ABCB1, ABCG2, and KLF4 might be considered as putative indicators for paclitaxel resistance in LSCC patients.
Differential Expression of Hypertension-Associated miRNAs in the Plasma of Patients with White Coat Hypertension
(Lippincott Williams & Wilkins, 2015) Cengiz, Mahir; Karatas, Omer Faruk; Koparir, Erkan; Yavuzer, Serap; Ali, Chayar; Yavuzer, Hakan; Ozen, Mustafa
White coat hypertension (WCH) is a high cardiovascular risk condition, and a fundamental understanding of the cause and pathophysiology of the disorder is still lacking. Recent studies demonstrated that microRNAs (miRNAs) are involved in hypertension; however, the roles of miRNAs in WCH are not known. The expressions of selected 10 miRNAs were investigated independently in plasma samples from 30 hypertension (HT) patients, 30 WCH patients, and 30 normotensive (NT) subjects. MiR-21, miR-122, miR-637, and let-7e expression levels were significantly upregulated in the HT group compared with the NT groups (P = 0.017, P = 0.022, P = 0.048, and P = 0.013, respectively). MiR-122 and miR-637 expressions were also significantly upregulated in the WCH group compared with the NT group (P = 0.048 and P = 0.039, respectively). MiR-296-5p expression level was significantly down-regulated in HT patients and upregulated in the WCH patients compared with the NT group (P = 0.049 and P = 0.039, respectively). Additionally, the ambulatory 24-hour and daytime systolic and diastolic blood pressures were negatively correlated with miR-2965p. MiR-296 and miR-637 had area under the curve (AUC) values of 0.778 and 0.774, respectively, which demonstrates their sufficiency to distinguish WCH from NT individuals. MiR-296 and miR-637 had AUC values of 0.868 and 0.680, respectively, which shows their potential to distinguish WCH from HT individuals. We report for the first time a plasma miRNA profile for WCH patients and demonstrate a novel link between miRNA and WCH. These findings may reveal crucial insights into the development of WCH.
The Effects of Daucus Carota Extract Against PC3, PNT1A Prostate Cells, Acetylcholinesterase, Glutathione S-Transferase, and Α-Glycosidase: An in Vitro-In Silico Study
(Wiley, 2021) Atalar, Mehmet Nuri; Aras, Abdulmelik; Turkan, Fikret; Barlak, Neslisah; Yildiko, Umit; Karatas, Omer Faruk; Alma, Mehmet Hakki
Daucus carota L. ssp. major (DCM) plant is widely used in traditional medicine to treat some types of cancer and various diseases. Therefore, we evaluated the biological activities of this plant to define its effects against prostate cancer (PCa), Alzheimer's disease (AD), oxidation, and diabetes mellitus (DM) as well as identified its phenolic composition. To determine the anti-cancer properties of the plant extract, we treated PCa cells with the extract at a concentration range of 0.25, 0.5, 1, 2, and 4 mg/ml. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. As a result of precise measurements at the millimolar level, it was observed that the plant extract showed an effective inhibition (IC50) against glutathione S-transferase (GST; 12.84 mM), acetyl cholinesterase (AChE; 15.07 mM), and alpha-Gly (11.75 mM) enzymes when compared with standard inhibitors. Antioxidant activities of DCM methanol extract were determined via two well-known in vitro techniques. The extracts showed antioxidant activities against the DPPH and ABTS(+). The LC-ESI-MS/MS was used to determine the phenolic compounds of methanol extract from DCM. Chlorogenic acid (2,089.096 mu g/g), shikimic acid (193.14 mu g/g), and coumarin (113.604 mu g/g) were characterized as major phenolic compounds. In addition, the interactions of chlorogenic acid, chrysin, coumarin, and shikimic acid with the used three enzymes have been calculated using molecular docking simulation. Practical applications Plant natural phenolic compounds have protective effects such as anti-inflammatory, antioxidant, anticarcinogen, and enzyme inhibitory. Therefore, it has an important place in the food and pharmaceutical industry. The present study aims to reveal the enzyme inhibitory, antioxidant, and anticarcinogenic properties of the Daucus carota ssp. Major (DCM) plant extract. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. DCM extract demonstrated considerable antioxidant activity and inhibitory potential on used metabolic enzymes. These biological effects are thought to have a relationship with rich chemical composition.
Erlotinib-Modified Bodipy Photosensitizers for Targeted Photodynamic Therapy
(Wiley-VCH Verlag GmbH, 2023) Gul, Elif Yildiz; Karatas, Elanur Aydin; Dogan, Hatice Aydin; Karatas, Omer Faruk; Cosut, Buenyemin; Ecik, Esra Tanriverdi
Photodynamic therapy (PDT) is an innovative, non-invasive and highly selective therapeutic modality for tumours and non-malignant diseases. BODIPY based molecules can function as new generation photosensitizers (PSs) in various PDT applications. Despite numerous conjugated PS systems are available, BODIPYs containing erlotinib lagged behind other photosensitizer units. In this study, smart photosensitizers containing BODIPY, erlotinib and hydrophilic units were prepared for the first time, their physicochemical properties and PDT effects were investigated. Compared with non-halogenated compound, halogenated derivatives possessed much lower fluorescence profile as well as the good ROS generation ability under red light. In vitro PDT studies were performed on both healthy (PNT1a) and prostate cancerous cells (PC3) to determine the selectivity of the compounds on cancerous cells and their effects under light. The halogenated conjugates, exposed to low dose of light illumination exhibited potent activity on cancer cell viability and the calculated IC50 values proved the high phototoxicity of the photosensitizers. It was also determined that the PSs have very low dark toxicity and that the light illumination and ROS formation are required for the initiation of the cell death mechanism. As a result, erlotinib modified BODIPYs could serve as promising agents in anticancer photodynamic therapy.