PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/8
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Article Citation - WoS: 2Citation - Scopus: 3Biological Activities of Etodolac-Based Hydrazone, Thiazolidinone and Triazole Derivatives on Breast Cancer Cell Lines MCF-7 and MDA-MB(Wiley, 2025) Sevinc, Sevgi Kocyigit; Cikla-Suzgun, Pelin; Tiber, Pinar Mega; Kucukguzel, S. Guniz; Orun, Oya; Güniz Küçükgüzel, Ş.In this study, several etodolac-based hydrazone, thiazolidinone, and triazole derivatives that we synthesized and characterized in our earlier research were tested against the hormone-responsive breast cell line MCF-7 and the triple-negative MDA-MB-231, as well as the murine origin fibroblast cell line L-929, at varying doses for their effects on cell viability and toxicity and for their inhibitory activity on cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) formation. Cell viability and apoptosis tests were utilized to assess the anti-cancer potential of etodolac and its derivatives after the cells were exposed to varied concentrations of synthesized compounds for three different time periods. ELISA and Western blot methods were used to detect protein levels. All synthesized compounds demonstrated higher anti-cancer activity at significantly lower doses compared to etodolac (half-maximal inhibitory concentration [IC50] of 0-50 mu M range in derivatives versus 0.5-1 mM range in etodolac). Except for SGK 242, which had a major toxic effect on all cells, the chemicals SGK 206 and SGK 217 had a twice-less impact on control murine L-929 fibroblasts. Similar to proliferation, low concentrations of SGK 206 and SGK 217 (25-50 mu M) significantly induced apoptosis in breast cancer cells but not in normal cells. Additionally, they inhibited COX-2 protein expression at 50 mu M, and SGK 206 inhibited PGE2 release more effectively than etodolac in cancer cells. The results of this study suggest that, in comparison to a healthy control group, the thiazolidinone derivative SGK 206 and the thiazolidinone derivative SGK 217 are more effective than etodolac when it comes to the breast cancer cell lines MCF-7 and MDA-MB-231. SGK 206 exhibits a low IC50 value, a distinct dose-response relationship, and strong apoptotic effects, particularly on MDA-MB-231 cells.Article Citation - WoS: 1Citation - Scopus: 2Glyphosate and AMPA-Induced Apoptosis and Epigenetic Alterations in HepG2 Cells: Upregulation of P53-BAX-CASP Pathways(Pergamon-Elsevier Science Ltd, 2025) Mehtiyev, Tugrul; Guler, Zeynep Rana; Aktan, Elif; Ozden, SibelGlyphosate and its metabolite aminomethylphosphonic acid (AMPA) are environmental contaminants with potential toxic effects. This study aimed to investigate apoptosis and epigenetic alterations induced by glyphosate and AMPA in HepG2 cells. The IC50 values for glyphosate and AMPA were 6.19 mM and 8.13 mM, respectively, following 24 h exposure; mechanistic assays were conducted at sub-cytotoxic concentrations (50-500 mu M). Annexin V/PI flow cytometry revealed that AMPA significantly increased early apoptosis (up to 116 %, p < 0.001), while glyphosate elevated late apoptosis (up to 145 %, p < 0.001). Gene expression analysis showed significant upregulation of p53 (>= 1.49-fold), BAX (>= 1.82-fold), CASP3 (>= 1.37-fold), and CASP9 (>= 1.83-fold), with no significant change in BCL2. Epigenetic analysis indicated that both glyphosate and AMPA increased global DNA methylation, with fold changes ranging from 1.43 to 1.62-fold at concentrations of 100-250 mu M (p < 0.05). DNA methyltransferase genes DNMT1 (>= 2.44-fold), DNMT3A (>= 1.65-fold), and DNMT3B (>= 1.65-fold) were upregulated. Additionally, histone modification profiling showed elevated levels of H3K27me3, H3K9me3, and H3K9ac (p < 0.05), alongside increased expression of G9a (>= 1.64-fold), EZH2 (>= 2.14-fold), SETD1B (>= 2.15-fold), HAT1 (>= 2.40-fold), and SIRT1 (>= 2.57-fold), and downregulation of SUV39H1 (>= 0.27-fold). These findings reveal the molecular mechanisms of glyphosate and AMPA toxicity, linking apoptosis to epigenetic alterations and enhancing understanding of their risks.Article Citation - WoS: 7Citation - Scopus: 9A Multi-Parameter Evaluation of the Neuroprotective and Cognitive-Enhancing Effects of <i>origanum Onites</I> L. (turkish Oregano) Essential Oil on Scopolamine-Induced Amnestic Rats(Springer/plenum Publishers, 2022) Aykac, Asli; Terali, Kerem; Ozbeyli, Dilek; Ede, Seren; Albayrak, Omercan; Baser, Kemal Husnu Can; Sener, GokselAlzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions (dementia) and represents a growing public health concern since the population in the age groups at risk is increasing. The latter raises an urgent need to translate research findings in the basic brain and behavioral sciences into anti-AD drugs and disease-modifying therapies. Origanum onites (L.), also called Turkish oregano, is a perennial and herbaceous plant species grown for centuries for medicinal, cosmetic and culinary purposes. This is the first study to investigate the putative neuroprotective and pro-cognitive activities of O. onites essential oil (OOEO) against scopolamine-induced amnesia of AD-type in Wistar albino rats. The results of behavioral tests revealed that OOEO administration was able to significantly alleviate learning and memory impairments induced by scopolamine in vivo. The observed effects could be attributed to inhibition of acetylcholinesterase activity, attenuation of oxidative stress and prevention of neuronal apoptosis in the hippocampus and frontal cortex of AD rats. Modulation of pro-inflammatory enzymes, including cyclooxygenase-2, inducible nitric oxide synthase and myeloperoxidase, might further contribute to the neuroprotective properties of OEOO, as predicted by our in silico models. These findings offer novel insights into the therapeutic potential of OEOO in patients with AD.