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    Differential Cytotoxic Activity of a New Cationic Pd(II) Coordination Compound with N4-Tetradentate Hybrid Ligand in Cancer Cell Lines
    (Istanbul University Press, 2022) Genel, M.E.; Selvi, S.; Yilmaz, I.; Akar, R.O.; Yaylim, I.; Sengul, A.; Ulukaya, E.
    Objective: Successful cancer treatment still requires the discovery of novel compounds that hold promise for chemotherapeutics. The objective of this study was to examine the effectiveness of a newly synthesized cationic palladium(II) coordination compound that functions via several pathways to provide an efficient therapeutic option for various cancer cells. Materials and Methods: A new cationic palladium(II) coordination compound, [Pd(L)]Cl2·H2O, denoted as Complex 1, where the ligand L is the compound 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine), was synthesized and characterized by the attenuated total reflectance (ATR)-fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), electrospray ionization mass spectrometry (ESI-MS), and carbon-hydrogen-nitrogen (CHN) analyses. The density functional theory (DFT) calculations show the coordination sphere around the metal center in Complex 1 to be made up of tertiary N atoms of the pyridine (py) and benzimidazole (bim) rings completing the square-planar geometry with significant distortion. The anti-growth/cytotoxic activity of the complex was determined using the sulforhodamine B (SRB) and adenosine triphosphate (ATP) viability assays for 24 and 48 h in vitro. The study evaluates the determinations for annexin V-propidium iodide (PI) positivity, mitochondrial membrane potential loss, Bcl-2 protein inactivation, and deoxyribonucleic acid (DNA) damage to investigate the cell death mode and its partial mechanism. Results: Complex 1 caused cytotoxicity in a dose-dependent manner in all the cell lines used, with IC50 values ranging from 2.6-8.8 ?M for 48 h. Among the cancer models, colon and breast cancer cell lines underwent cell death by well-described apoptosis through the intrinsic pathway involving the mitochondria. However, the other cell lines did not show such a cell death modality. This implies that differential cell death modes operate based on the cancer type. Conclusion: For the treatment of breast and colon cancers, the complex 1 appears to be a unique, promising complex. Therefore, complex 1 deserves further attention for proof of concept in animal models. © 2022, Istanbul University Press. All rights reserved.
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    Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin
    (Springer, 2015) Dogan, Z.; Kocahan, S.; Erdemli, E.; Kose, E.; Yilmaz, I.; Ekincioglu, Z.; Ekinci, N.
    Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p < 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p < 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.