Person: YILMAZ, VEYSEL TURAN
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YILMAZ
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VEYSEL TURAN
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Publication Palladium (II)-based novel approach to kill cancer stem cells of breast cancer(Oxford Univ Press, 2015-12-01) Ulukaya, Engin; Aydınlık, Seyma; Erkısa, Merve; Arı, Ferda; Yılmaz, Veysel Turan; Ulukaya, Engin; Aydınlık, Seyma; Erkısa, Merve; ARI, FERDA; YILMAZ, VEYSEL TURAN; Tıp Fakültesi; Kimya Bölümü; 0000-0003-4875-5472; 0000-0002-3127-742X; 0000-0002-6729-7908; 0000-0002-2849-3332; AAG-7012-2021; L-7238-2018; AAM-1001-2020; K-5792-2018; CEV-4436-2022Publication Novel 5-fluorouracil complexes of Zn(II) with pyridine-based ligands as potential anticancer agents(Royal Soc Chemistry, 2022-03-02) İcsel, Ceyda; Yılmaz, Veysel T.; Aygün, Muhittin; Erkısa, Merve; Ulukaya, Engin; İÇSEL YILMAZ, CEYDA; YILMAZ, VEYSEL TURAN; Fen Edebiyat Fakültesi; Kimya Bölümü; 0000-0002-2849-3332; AAI-3342-2021; L-7238-2018A series of novel Zn(II) complexes of 5-fluorouracilate (5-FU), namely (Zn(5-FU)(2)(bpy)] (1), [Zn(5-FU)(2)(phen)] (2), [Zn(5-FU)(2)(dpya)]center dot H2O (3), [Zn(5-FU)(2)(bpyma)]center dot 2H(2)O (4) and [Zn(5-FU)(2)(terpy)]center dot H2O(5), were synthesized and structurally characterized by spectroscopic methods and X-ray crystallography. 5-FU was coordinated to Zn(II) via the deprotonated N3 site and also presented the N1 and N3 linkage isomerism in 4 and 5 due to its tautomerism. The antiproliferative activity of the complexes was studied against lung (A549), breast (MDA-MB-231), colon (HCT116) and prostate (DU145) cancer cell lines. Complexes 1, 4 and 5 except 2 and 3 showed potent growth inhibitory activity towards selected cancer cells. Remarkably, 4 was highly cytotoxic towards A549 and MDA-MB-231 cell lines, being more active than the clinical drugs cisplatin and 5-FU. In addition, 4 was not toxic to normal lung cells (BEAS-2B). The complex exhibited a significantly high affinity towards DNA as assessed by gel electrophoresis and DNA docking. The mechanistic studies of 4 in A549 cells indicated that the complex induced apoptotic cell death as evidenced via caspase 3/7 activity, Bcl2 inactivation, annexin V and DAPI/PI staining. 4 further elevated the levels of reactive oxygen species (ROS), depolarized mitochondria and enhanced the expression of gamma-H2AX, thus contributing to its remarkable anticancer activity.Publication Unfolded protein response is involved in trans-platinum (ii) complex-induced apoptosis in prostate cancer cells via ros accumulation(Bentham Science Publ Ltd, 2019-01-01) Karakaş, Didem; Cevatemre, Buse; Oral, Arzu Y.; YILMAZTEPE ORAL, ARZU; Yılmaz, Veysel T.; YILMAZ, VEYSEL TURAN; Ulukaya, Engin; Tıp Fakültesi; Biyokimya Ana Bilim Dalı; 0000-0002-3781-6834; 0000-0002-8962-9758; 0000-0002-2849-3332; AHD-2050-2022; KMA-2321-2024; A-5841-2017; L-7238-2018; L-6682-2018Background: Prostate cancer is one of the most common cancer types and it is the sixth leading cause of cancer-related death in men worldwide. Even though novel treatment modalities have been developed, it still a lifethreatening disease. Therefore novel compounds are needed to improve the overall survival.Methods: In our study, it was aimed to evaluate the anti-cancer activity of newly synthesized Platinum (II) [Pt(II)] complex on DU145, LNCaP and PC-3 prostate cancer cell lines. The cytotoxic activity of Pt(II) complex was tested by SRB and ATP cell viability assays. To detect the mode of cell death; fluorescent staining, flow cytometry and western blot analyses were performed.Results: The Pt(II) complex treatment resulted in a decrease in cell viability and increasing levels of apoptotic markers (pyknotic nuclei, annexin-V, caspase 3/7 activity) and a decrease in mitochondrial membrane potential in a dose dependent manner. Among cell types, tested PC-3 cells were found to be more sensitive to Pt(II) complex, demonstrating elevation of DNA damage in this cell line. In addition, Pt(II) complex induced Endoplasmic Reticulum (ER) stress by triggering ROS generation. More importantly, pre-treatment with NAC alleviated Pt(II) complex-mediated ER stress and cell death in PC-3.Conclusion: These findings suggest an upstream role of ROS production in Pt(II) complex-induced ER stressmediated apoptotic cell death. Considering the ROS-mediated apoptosis inducing the effect of Pt(II) complex, it warrants further evaluation as a novel metal-containing anticancer drug candidate.Publication Synthesis and crystal structures of new di- and polynucicar silver(I) saccharinatc complexes with tertiary monophosphanes(Int Union Crystallography, 2015-01-01) Büyükgüngör, Orhan; Yılmaz, Veysel Turan; YILMAZ, VEYSEL TURAN; Fen Edebiyat Fakültesi; Kimya Bölümü; 0000-0002-2849-3332; L-7238-2018Publication Two fluorescent silver(i)-saccharinato complexes of 2-methylpyrazine and pyrazine-2-carboxamide with ag...ag interactions(Elsevier, 2008-11-01) Şenel, Evrim; Kazak, Canan; Yılmaz, Veysel T.; YILMAZ, VEYSEL TURAN; Güney, Emel; 0000-0002-2849-3332; 0000-0003-2475-8775; L-7238-2018; S-1281-2017Two new silver(I)-saccharinato (sac) complexes [Ag-4(sac)(4)(mpyz)(2)(H2O)(2)] (1), and [Ag-2(sac)(2)(pyzca)(2)] (2), (mpyz = 2-methylpyrazine, pyzca = pyrazine-2-carboxamide) have been synthesized and structurally characterized. Bridging of silver(l) centers by sac ligands results in argentophilic contacts of 3.192(1) angstrom for 1, and 3.168(2) angstrom for 2. These Ag...Ag interactions were discussed in terms of bond distances and angles around the silver(l) ion. Both complexes exhibit strong blue luminescence at room temperature in the solid state.Publication Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress-induced apoptosis(Springer, 2019-10-26) İçsel, Ceyda; Yılmaz, Veysel T.; Cevatemre, Buse; Aygün, Muhittin; Ulukaya, Engin; İÇSEL YILMAZ, CEYDA; YILMAZ, VEYSEL TURAN; Fen Edebiyat Fakültesi; Kimya Bölümü; 0000-0002-2849-3332; L-7238-2018; AAI-3342-2021A series of the structurally related platinum(II) saccharinate (sac) complexes with alkylphenylphosphines, namely cis-[Pt(sac)(2)(PPh2Me)(2)]center dot DMSO (1), cis-[Pt(sac)(2)(PPhMe2)(2)] (2), cis-[Pt(sac)(2)(PPh2Et)(2)] (3), and cis-[Pt(sac)(2)(PPhEt2)(2)]center dot 2DMSO (4), were synthesized and fully characterized; their structures were determined by X-ray crystallography. All the complexes were investigated for their anticancer potentials on three human cancer cells including A549 (lung), MCF-7 (breast), and HCT116 (colon) in addition to a noncancerous human bronchial epithelial cells (BEAS-2B). Specifically, 1 and 3 showed significant cytotoxic effects against MCF-7 and HCT116 cell lines in comparison to cisplatin, and were considered as the most potent ones in the series. The cytotoxic complexes were found to cleave DNA efficiently. In addition, the binding interactions of the complexes with DNA were confirmed by enzyme inhibition and molecular docking studies. Complexes 1 and 3 were capable of inducing apoptosis and arrested the cell cycle at the DNA synthesis (S) phase in MCF-7 cells. Furthermore, 1 and 3 caused the excessive generation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and double-strand DNA breaks.Publication Combination of histone deacetylase inhibitor with cu(ii) 5,5-diethylbarbiturate complex induces apoptosis in breast cancer stem cells: A promising novel approach(Bentham Science, 2021-01-01) Erkisa, Merve; Aztopal, Nazlihan; Erturk, Elif; Ulukaya, Engin; Yilmaz, Veysel T.; Ari, Ferda; Erkisa, Merve; Aztopal, Nazlihan; YILMAZ, VEYSEL TURAN; Ari, Ferda; ARI, FERDA; ertürk; Fen Edebiyat Fakültesi; 0000-0002-3127-742X; 0000-0003-3118-8061; 0000-0002-2849-3332; 0000-0002-6729-7908; JQI-3400-2023; AAM-1001-2020; L-7238-2018; AAG-7012-2021; L-6687-2018Background: Cancer Stem Cells (CSCs) are a subpopulation within the tumor that play a role in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy.Objective: In our study, we scope out the effects of a combination of a histone deacetylases inhibitor, Valproic Acid (VPA), and Cu(II) complex [Cu(barb-kappa N)( barb-kappa 2N,O)(phen-kappa N,N')]center dot H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7).Methods: The viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2',7'-dichlorofluorescein diacetate staining.Results: The VPA combined with Cu(II) complex showed anti-proliferative activity on MCF-7s cells in a dose-and time-dependent manner. Treatment with a combination of 2.5 mM VPA and 3.12 mu M Cu(II) complex induced oxidative stress in a time-dependent manner, as well as apoptosis evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels.Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy for which further analysis is required.