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  1. Ana Sayfa
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Yazar "Tosun, Nazan Goksen" seçeneğine göre listele

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  • [ X ]
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    A Silver Compound with Potential Applications as an Anticancer, Antibacterial, Antifungal, and Anti-Alzheimer's Agent
    (Wiley-V C H Verlag Gmbh, 2023) Korkmaz, Nesrin; Kisa, Dursun; Kaplan, Ozlem; Tosun, Nazan Goksen; Ozgur, Aykut; Imamoglu, Rizvan; Karadag, Ahmet
    This study investigated the biological activity of the silver coordination compound K-22. The IC50 values of K-22 on cancer cell lines range from 0.797 mu g/mL to 3.426 mu g/mL, indicating that K-22 might preferably inhibit A549, Saos-2, MCF-7, and HT-29 cell proliferation and thus have better therapeutic activity. Furthermore, K-22 stimulated apoptosis via up-regulation of the mRNA and protein expression level of Bax/Bcl-2 ratio in A549, Saos-2, MCF-7, and HT-29. K-22 exhibited antimicrobial activity against S. aureus, E. faecalis, K. pneumonia, P. aeruginosa, C. utilis, and C. albicans. Experimental results show that the compound has inhibitory potential with an IC50 value of 178.10 mu M for the BChE (butyrylcholinesterase) enzyme, which has a vital role in the progression of Alzheimer's disease. As a result, compound K-22 exhibits a strong potential for medical use due to its anticancer, antibacterial, antifungal, and anti-Alzheimer properties.
  • [ X ]
    Öğe
    Dual targeting of HSP90 and BCL-2 in breast cancer cells using inhibitors BIIB021 and ABT-263
    (Springer, 2025) Tosun, Nazan Goksen; Kaplan, Ozlem
    Purpose:The incidence of breast cancer has been increasing in recent years, and monotherapy approaches are not sufficient alone in the treatment of breast cancer. In the combined therapy approach, combining two or three different agents in lower doses can mitigate the side effects on living cells and tissues caused by high doses of chemical agents used alone. ABT-263 (navitoclax), a clinically tested Bcl-2 family protein inhibitor, has shown limited success in clinical trials due to the development of resistance to monotherapy in breast cancer cells. This resistance shows that monotherapy approaches are inadequate and more effective treatment strategies are needed. It is the ability of HSP90 inhibitors to destabilize many oncoproteins that are critical for the survival of cancer cells. This study aimed to examine the anticancer activity of the combination of ABT-263 with BIIB021, a new generation HSP90 inhibitor, on two widely used breast cancer cell lines: MCF-7 (ER-positive) and MDA-MB-231 (triple-negative breast cancer, TNBC). These cell lines were selected to represent distinct breast cancer subtypes with different molecular characteristics and clinical behaviors.Methods: Single and combined cytotoxic effects of this agents on MCF-7 and MDA-MB-231 breast cancer cell lines were determined using the MTT cell viability test. The combined use of these two agents showed a synergistic effect, and this effect was assigned using the Chou and Talalay method. mRNA and protein levels of apoptosis-related genes Bax, Bcl-2, Casp9, and Heat Shock Proteins HSP27, HSP70, and HSP90 were analyzed using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively.Results:The cytotoxicity analysis, combined with the application of the Chou-Talalay method, demonstrated that the BIIB021 and ABT-263 combination exhibited significantly greater anticancer activity compared to the individual effects of either BIIB021 or ABT-263 in breast cancer cell lines. The analysis of mRNA and protein levels indicated that the BIIB021+ABT-263 combination may have triggered the intrinsic apoptotic pathway in breast cancer cells.Conclusion: This study showed that co-administration of ABT-263 and BIIB021 agents exhibited synergistic cytotoxic effects and increased the expression of apoptosis-related genes in breast cancer cell lines
  • [ X ]
    Öğe
    Efficacy of the greenly synthesized silver, copper, and nickel nanoparticles using Allium tuncelianum extract against Acanthamoeba castellanii
    (Elsevier, 2023) Aykur, Mehmet; Tosun, Nazan Goksen; Kaplan, Ozlem; Ozgur, Aykut
    Acanthamoeba is a common protozoan in many environments, leading to infection in humans and animals. Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE) are caused by Acanthamoeba. AK is an infection in the eye that can lead to vision loss and does not have a fully effective treatment. Therefore, there is an urgent need to develop new therapies against Acanthamoeba for the treatment of AK and GAE. Green nanotechnology synthesis approaches have been recently reported to be more environmentally friendly and effective in antimicrobial, antiviral, antifungal, and antiprotozoal activities. Therefore, they might be a good strategy for developing anti-Acanthamoeba substances. This study aimed to use the microwave-assisted method to prepare AgNPs, CuNPs, and NiNPs using the crude extract of Allium tuncelianum (AT). Moreover, the synthesized AT-AgNPs, AT-CuNPs, and AT-NiNPs were characterized using UV-Visible spectroscopy, DLS, and FTIR tech-niques. The first time anti-amoebic activity of AT-AgNPs, AT-CuNPs, and AT-NiNPs was evaluated against Acanthamoeba castellanii. Anti-amoebic activity as IC50 value of AT-AgNPs, AT-CuNPs, and AT-NiNPs was observed 1556.56 +/- 7.36 mu g/ml, 1826.44 +/- 17.84 mu g/ml, and 2014.23 +/- 7.04 mu g/ml after 24 h, respectively. After 24 h, AT-AgNPs were shown to be superior to other NPs in killing Acanthamoeba trophozoites at a 2000 mu g/ ml concentration. AT-AgNPs' IC50 value was determined to be effective against Acanthamoeba trophozoites at a concentration almost twice as low as PVP-I's IC50 value after 48 h. At doses of 500 mu g/ml, 1000 mu g/ml, and 2000 mu g/ml, the impact of AT-AgNPs on the viability of 50% Acanthamoeba trophozoites was assessed after 48 h. The conclusion of the present study demonstrates the most effective of AT-AgNPs among the nanoparticles when used against the treatment of infections caused by A. castellanii. These agents show the potential to create new, efficient, and secure treatment options.
  • [ X ]
    Öğe
    Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line
    (Humana Press Inc, 2024) Kaplan, Ozlem; Tosun, Nazan Goksen
    Neuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.

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