WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Citation - WoS: 2Citation - Scopus: 2Effects of Golden Thistle (scolymus Hispanicus L.) on Cytotoxic Activity: Cell Cycle Arrest and Apoptotic Properties on the Caco-2 Cell Line(Mary Ann Liebert Inc., 2022) Özel Taşcı, Cansu; Güleç, ŞükrüCancer is a global concern for many individuals with high mortality rates, with colon cancer being the third most common diagnosed cancer worldwide. A phytochemical-rich diet is often recommended in the prevention and during the treatment of cancer cases. Golden thistle (GT) plant (Scolymus hispanicus L.) is a wild edible plant widely consumed in the Mediterranean countries. In this study, we aimed to obtain a hydromethanolic extract from three parts of the GT plant and test its antiproliferative activity in the CaCo-2 human adenocarcinoma cell line. Concentrations of the golden thistle extract (GTE) were used to treat CaCo-2 cells and the most significant reduction was detected with 4 mg/mL GTE after 72 h, with 78.3% decrease in cell viability (P < .05). Additionally, 4 mg/mL GTE caused 7.8-fold higher release of lactate dehydrogenase enzyme, indicating cell death after treatment. Flow cytometric analyses concluded both 3.3-fold higher early and late apoptotic activity of the 4 mg/mL GTE compared with the nontreated control group (P < .05). Last, 4 mg/mL GTE showed 24.1% reduction in the G1 phase and 38.1% increase in the S phase of cell cycle distribution. The alteration of G1 and S phases in the cell cycle led to growth reduction of CaCo-2 cells and caused apoptosis. CopyrightArticle Citation - WoS: 9Citation - Scopus: 10An Answer To Colon Cancer Treatment by Mesenchymal Stem Cell Originated From Adipose Tissue(Mashhad University of Medical Sciences, 2018) İplik, Elif Sinem; ERtuğrul, Barış; Kozanoğlu, İlknur; Baran, YusufObjective(s): Colon cancer is risen up with its complex mechanism that directly impacts on its treatment as well as its common prevalence. Mesenchymal stem cells (MSCs) have been considered as a therapeutic candidate for conventional disease including cancer. In this research, we have focused on apoptotic effects of adipose tissue-derived MSCs in colon cancer. Materials and Methods: MSCs were obtained from adipose tissue and characterized by Flowcytometer using suitable antibodies. MSCs, HT-29, HCT-116, RKO and healthy cell line MRC5 were cultured by different seeding procedure. After cell viability assay, changes in caspase 3 enzyme activity and the level of phosphatidylserine were measured. Results: For cell viability assay, a 48 hr incubation period was chosen to seed all cells together. There was a 1.36-fold decrease in caspase 3 enzyme activity by co-treatment of RKO and MSCs in addition to 2.02-fold decrease in HT-29 and MSCs co-treatment, and 1.103-fold increase in HCT-116 and MSCs. The results demonstrated that HCT-116 led to the highest rate of apoptotic cell death (7.5%) compared with other cells. Conclusion: We suggest that MSCs might remain a new treatment option for cancer by its differentiation and repair capacity.Article Citation - WoS: 28Citation - Scopus: 29Revealing Genome-Wide Mrna and Microrna Expression Patterns in Leukemic Cells Highlighted “hsa-Mir as a Tumor Suppressor for Regain of Chemotherapeutic Imatinib Response Due To Targeting Stat5a(SAGE Publications Inc., 2015) Tezcanlı Kaymaz, Burçin; Selvi Günel, Nur; Ceyhan, Metin; Bozok Çetintaş, Vildan; Özel, Buket; Kartal Yandım, Melis; Kıpçak, Sezgi; Aktan, Çağdaş; Adan Gökbulut, Aysun; Baran, Yusuf; Kosova Can, BuketBCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNAArticle Citation - WoS: 20Citation - Scopus: 23Apoptotic Effects of Non-Edible Parts of Punica Granatum on Human Multiple Myeloma Cells(SAGE Publications Inc., 2016) Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, YusufMultiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.Article Citation - WoS: 43Citation - Scopus: 49The Pleiotropic Effects of Fisetin and Hesperetin on Human Acute Promyelocytic Leukemia Cells Are Mediated Through Apoptosis, Cell Cycle Arrest, and Alterations in Signaling Networks(SAGE Publications Inc., 2015) Adan, Aysun; Baran, YusufFisetin and hesperetin, flavonoids from various plants, have several pharmaceutical activities including antioxidative, anti-inflammatory, and anticancer effects. However, studies elucidating the role and the mechanism(s) of action of fisetin and hesperetin in acute promyelocytic leukemia are absent. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by fisetin and hesperetin on human HL60 acute promyelocytic leukemia cells. The viability of HL60 cells was evaluated using the MTT assay, apoptosis by annexin V/propidium iodide (PI) staining and cell cycle distribution using flow cytometry, and changes in caspase-3 enzyme activity and mitochondrial transmembrane potential. Moreover, we performed whole-genome microarray gene expression analysis to reveal genes affected by fisetin and hesperetin that can be important for developing of future targeted therapy. Based on data obtained from microarray analysis, we also described biological networks modulated after fisetin and hesperetin treatment by KEGG and IPA analysis. Fisetin and hesperetin treatment showed a concentration- and time-dependent inhibition of proliferation and induced G2/M arrest for both agents and G0/G1 arrest for hesperetin at only the highest concentrations. There was a disruption of mitochondrial membrane potential together with increased caspase-3 activity. Furthermore, fisetin- and hesperetin-triggered apoptosis was confirmed by annexin V/PI analysis. The microarray gene profiling analysis revealed some important biological pathways including mitogen-activated protein kinases (MAPK) and inhibitor of DNA binding (ID) signaling pathways altered by fisetin and hesperetin treatment as well as gave a list of genes modulated ≥2-fold involved in cell proliferation, cell division, and apoptosis. Altogether, data suggested that fisetin and hesperetin have anticancer properties and deserve further investigation.Article Citation - WoS: 13Citation - Scopus: 15In Vitro Evaluation of Doxorubicin-Incorporated Magnetic Albumin Nanospheres(John Wiley and Sons Inc., 2014) Zeybek, Ayça; Şanlı Mohamed, Gülşah; Ak, Güliz; Yılmaz, Habibe; Şanlıer, Şenay H.Magnetic albumin nanospheres that incorporate doxorubicin (M-DOX-BSA-NPs) were prepared previously by our research group to develop magnetically responsive drug carrier system. This nanocarrier was synthesized as a drug delivery system for targeted chemotherapy. In this work, cytotoxic effects of doxorubicin (DOX)-loaded/unloaded or magnetic/non-magnetic nanoparticles and free DOX against PC-3 cells and A549 cells were determined with the MTT test and the results were compared with each other. DOX-loaded magnetic albumin nanospheres (M-DOX-BSA-NPs) were found more cytotoxic than other formulations. The quantitative data obtained from flow cytometry analysis further verified the higher targeting and killing ability of M-DOX-BSA-NPs than free DOX on both of the cancer cell lines. Additionally, the results of cell cycle analysis have showed that M-DOX-BSA-NPs affected G1 and G2 phases. Finally, cell images were obtained using spin-disk confocal microscopy, and cellular uptake of M-DOX-BSA-NPs was visualized. The findings of this study suggest that M-DOX-BSA-NPs represent a potential doxorubicin delivery system for targeted drug transport into prostate and lung cancer cells. In this study, we found that M-DOX-BSA-NPs provide many advantages as targeted drug delivery, enhanced drug killing ability and bioavailability based on cytotoxicity, flow cytometry, and confocal microscopy image results.Article Citation - WoS: 2Citation - Scopus: 3A Novel Natural Product, Kl-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells(Turkish Society of Hematology, 2015) Adan Gökbulut, Aysun; Yaşar, Mustafa; Baran, YusufObjective: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by naturin natural Products, İzmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. Materials and Methods: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. Results: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. Conclusion: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.Article Citation - WoS: 10Citation - Scopus: 14Enalapril-Induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves Stat5a(International Institute of Anticancer Research, 2012) Purçlutepe, Özlem; İskender, Güniz; Kiper, Hatice Demet; Tezcanlı, Burçin; Selvi, Nur; Biray Avcı, Çığır; Kosova, Buket; Adan Gökbulut, Aysun; Şahin, Fahri; Baran, Yusuf; Saydam, GürayBackground: In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death. Materials and Methods: Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5- carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose-and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls. Conclusion: Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.Article Citation - WoS: 33Citation - Scopus: 37Apoptotic Effects of Quercitrin on Dld-1 Colon Cancer Cell Line(Springer Verlag, 2014) Çinçin, Zeynep Birsu; Ünlü, Miray; Kıran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Çakmakoğlu, BediaQuercetin, 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.Article Citation - WoS: 27Citation - Scopus: 27New Indication for Therapeutic Potential of an Old Well-Known Drug (propranolol) for Multiple Myeloma(Springer Verlag, 2013) Kozanoğlu, İlknur; Kartal Yandım, Melis; Çinçin, Zeynep Birsu; Özdoğu, Hakan; Çakmakoğlu, Bedia; Baran, YusufPurpose: Propranolol, a non-selective β-adrenergic receptor blocker, has been used for the treatment of the patients with hypertension for more than 50 years. There are several in vitro and in vivo evidences that β-adrenergic receptor antagonists inhibit proliferation and angiogenesis and also increase apoptosis in breast, skin, and colon cancers. The aim of this study was to investigate the cytotoxic and apoptotic effects of propranolol and the genes involved in propranolol-induced apoptosis in multiple myeloma cells. Methods: Time-dependent antiproliferation and apoptotic effects of propranolol were subsequently determined by MTT cell proliferation assay, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and also the localization of phosphatidylserine in the plasma membrane. Changes in expression levels of NF-ΚB pathway were examined by qRT-PCR array. Results: IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 μM after 24-, 48-, and 72-h propranolol exposure, respectively. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to propranolol in U266 cells in a time- and dose-dependent manner. There were increases in expression levels of BCL10, TRAF family members, interleukins, TLR1-4, TNFRSF10B, NF-κB, and the inhibitors of NF-κB genes, and significant decreases in expression levels of Bcl-2 in response to propranolol treatment were observed. Conclusion: These results revealed that propranolol has antiproliferative and apoptotic effects on multiple myeloma cells. Being supported with in vivo analyses, propranolol can be a good and economical way to treat multiple myeloma patients.