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    Apoptosis-inducing, anti-angiogenic and anti-migratory effects of a dinuclear Pd(II) complex on breast cancer: A promising novel compound
    (Academic Press Inc Elsevier Science, 2024) Genel, Merve Erkisa; Adacan, Kaan; Selvi, Selin; Kutucu, Deniz Erol; Uvez, Ayca; Armutak, Elif Ilkay; Sengul, Abdurrahman
    Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer.
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    A Comparative Study on In vitro Anti-cancer and In vivo Anti-angiogenic Effects of TRPC Blockers Pyr-3 and SKF-96365
    (Bentham Science Publ Ltd, 2023) Kiyan, Hulya Tuba; Uvez, Ayca; Erkisa, Merve; Ikitimur-Armutak, Elif Ilkay; Yilmazer, Nadim; Esener, Osman Behzat Burak; Kutucu, Deniz Erol
    Introduction Angiogenesis is involved in many physiological and pathological conditions including cancer. A number of TRP channels induce angiogenesis, promote cell proliferation or induce apoptosis in several types of human cancers. Therefore, TRP channels may be considered potential pharmacological targets for therapeutic options of disorders caused by insufficient angiogenesis or aberrant vascularization. Aims This study aimed to comparatively investigate in vitro anti-cancer and in vivo anti-angiogenic effects of TRPC blockers Pyr-3 and SKF-96365. Methods For anti-cancer effects, four cancer cell lines (MDA-MB-231, A549, PC-3, and HCT-116) were used. In vivo anti-angiogenic effects were investigated by employing in vivo CAM assay of fertilized hen eggs. Results Pyr-3 affected cell viability in a dose-dependent manner, all concentrations of SKF-96365 significantly reduced cell viability in all cell lines. Pyr-3 and SKF-96365 at concentrations of 2.5 & mu;g/pellet and 50 & mu;g/pellet, respectively inhibited in vivo angiogenesis significantly. Conclusion The concentration of 2.5 & mu;g/pellet caused no irritation, whereas 50 & mu;g/pellet produced some slight irritation. Apart from their anti-cancer effects, our findings indicate that Pyr-3 and SKF-96365 may be promising anti-angiogenic agents for the treatment of angiogenesis-related disorders.
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    Effects of combined administration of doxorubicin and chloroquine on lung pathology in mice with solid Ehrlich ascites carcinoma
    (2022) Utkusavas, Ayfer; Gurel Gurevin, Ebru; Yilmazer, Nadim; Uvez, Ayca; Oztay, Fusun; Bulut, Huri
    Combined use of a chemotherapeutic agent and an autophagy inhibitor is a novel cancer treatment strategy. We investigated the effects of chloroquine (CQ) on lung pathology caused by both solid Ehrlich ascites carcinoma (EAC) and doxorubicin (DXR). A control group and eight experimental groups of adult female mice were inoculated subcutaneously with 2.5 × 106 EAC cells. DXR (1.5 mg/kg and 3 mg/kg) and CQ (25 mg/kg and 50 mg/kg) alone or in combination were injected intraperitoneally on days 2, 7 and 12 following inoculation with EAC cells. Lung tissue samples were examined using immunohistochemistry (IHC) for endothelial (eNOS), inducible nitric oxide synthase (iNOS) and neutrophil gelatinase-associated lipocalin (NGAL). Serum catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using ELISA. We found decreased levels of iNOS and eNOS in the groups that received 1.5 mg/kg DXR alone and in combination with 25 mg/kg and 50 mg/kg CQ. Combined administration of DXR and CQ partially prevented disruption of alveolar structure. Levels of antioxidant enzymes and MDA were lower in all treated groups; the greatest reduction was observed in mice that received the combination of 25 mg/kg CQ + 1.5 mg/kg DXR. Levels of NGAL were elevated in all treated groups. We found that CQ ameliorated both EAC and DOX induced lung pathology in female mice with solid EAC by reducing oxidative stress.