WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
Browse
8 results
Search Results
Article Ibuprofen and Nimesulide Derivatives Selectively Induce Apoptosis in HER2-Positive Breast Cancer via Inhibition of the PLA2-COX-2-NF-κB Pathway(Springer, 2026) Bedir, Ipek; Cakirli, Egemen; Kucukguzel, S. Guniz; Yilmaz, Ozgur; Biliz, Yagmur; Telci, DilekBackground Chronic inflammation contributes to breast cancer development through the phospholipase A(2) (PLA(2))-cyclooxygenase-2 (COX-2)-nuclear factor kappa B (NF-kappa B) cascade, which regulates prostaglandin synthesis, oxidative stress, and transcription of pro-inflammatory and anti-apoptotic genes. This pathway is particularly active in HER2-positive breast cancer, promoting proliferation, invasion, and resistance to apoptosis. Non-steroidal anti-inflammatory drugs such as ibuprofen and nimesulide target COX enzymes and have shown potential in suppressing inflammation-driven tumorigenesis. In this study, we evaluated the anticancer and anti-inflammatory activity of newly synthesized, structurally modified ibuprofen and nimesulide derivatives designed to modulate PLA(2)-COX-2-NF-kappa B axis. Methods and Results Cytotoxicity was assessed in HER2-positive breast cancer cells (AU565 and SKBR3) and compared with normal dermal fibroblasts (HDF) and breast epithelial cells (MCF-12A), using WST-1 assays. Apoptosis, cell cycle distribution, caspase-3/7 activation, and ROS generation were analyzed by imaging-based assays, flow cytometry, and fluorescence methods. Gene expression of PLA2G2A and PTGS2 was quantified by qRT-PCR, and NF-kappa B translocation was analyzed by immunocytochemistry. Two ibuprofen triazole derivative (D1) and ibuprofen thioether derivative (D7) and one nimesulide derivative (D8) significantly reduced cell viability in a dose-dependent manner without affecting normal cells. These derivatives induced G(0)/G(1) arrest, caspase-3/7 activation, ROS reduction, and increased late apoptosis. Downregulation of PLA2G2A and PTGS2 expression and inhibition of NF-kappa B translocation confirmed disruption of the PLA(2)-COX-2-NF-kappa B cascade. Conclusion These findings demonstrate that structurally optimized ibuprofen and nimesulide derivatives exert dual anti-inflammatory and anticancer effects in HER2-positive breast cancer by suppressing PLA(2)-COX-2-NF-kappa B pathway and promoting apoptotic cell death.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: 5Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats by Regulating Oxidative Stress(Marmara Univ, inst Health Sciences, 2023) Hersek, Irem; Koroglu, M. Kutay; Coskunlu, Busra; Ertas, Busra; Sener, Goksel; Ercan, Feriha; Köroğlu, KutayObjective: The purpose of this study was to examine the effects of apocynin (APC), an inhibitor of NADPH oxidase (NOX), on high-fat diet (HF)induced testis cytotoxicity.Methods: Wistar albino rats were divided into three groups as control, HF and HF+APC groups. Rats in HF and HF+APC groups were fed using HF for 16 weeks and in the last four weeks of this period vehicle solution or APC (25 mg/kg) was administered orally five days a week, respectively. Control group was fed with standart lab chow for 16 weeks. Cholesterol, triglyceride, high-density lipoproteins, leptin, estrogen, testosterone, LH and FSH were estimated in blood serum. Sperm parameters were analysed from the epididymis. Testicular malondialdehyde, 8-hydroxy-2deoxyguanosine, glutathione, superoxide dismutase and myeloperoxidase levels were estimated biochemically. Testicular morphology, proliferative, apoptotic and NOX2-positive cells were analysed histologically.Results: HF-induced obesity caused significant alterations in serum lipid and hormone profiles. Testicular malondialdehyde, 8-hydroxy-2deoxyguanosine, and myeloperoxidase levels increased, glutathione and superoxide dismutase levels decreased in this group. Moreover, altered sperm parameters, increased degenerated seminiferous tubules, apoptotic and NOX2 - positive cells and decreased proliferative cells were observed in the HF group. All these biochemical and histological alterations improved in the HF+APC group.Conclusion: HF-induced obesity causes altreations in lipid values, sperm parameters and testicular morphology by increasing oxidative stress through NOX2 activity. Apocynin might prevent testis damage via regulating oxidant/antioxidant balance.Article Citation - WoS: 14Citation - Scopus: 12Synthesis of Some Novel Hydrazide-Hydrazones Derived From Etodolac as Potential Anti-Prostate Cancer Agents(Marmara Univ, 2022) Koc, Hande Cevher; Atlihan, Irem; Mega-Tiber, Pinar; Orun, Oya; Kucukguzel, S. Guniz; Tiber, Pinar Mega(R,S)-Etodolac [1,8-diethyl-1,3,4,9-tetrahydrapyrano(3,4-b)indole-1-acetic acid] is a nonsteroidal anti-inflammatory drug that contains carboxylic acid group with the structure of pyrano[3,4-h]indole. In this study, a series of novel (R,S)-Etodolac derivatives (3a-1) bearing hydrazide-hydrazone moiety were synthesized. The structures of these compounds were characterized by spectral (H-1-NMR and FT-IR analyses) methods. All synthesized compounds were screened for anticancer activity against androgen-independent prostate adenocarcinoma (PC-3, DU-145) and androgen-dependent prostate adenocarcinoma (LNCaP) cell lines by using WST-8 colorimetric method. This method was used for cell viability and cytotoxicity analysis. Compound 3b (SGK-720) [2-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(2,6-dichlorophenyl)methylene]hydrazides] showed 10.36, 5.24, 15.53 mu M anticancer activity against PC3, DU145, LNCaP cancer cell lines, respectively. According to JC-1 mitochondrial membrane potential test and Annexin V/PI staining, 3b was found to have apoptotic effect on these cancer cells. It is concluded that compound 3b containing 2,6-dichloro substituents may be one of the candidate molecules to cope with prostate cancer.Article Citation - WoS: 18<i>petroselinum Crispum</I> Extract Ameliorates Scopolamine-Induced Cognitive Dysfunction: Role on Apoptosis, Inflammation and Oxidative Stress(Tsinghua Univ Press, 2022) Sener, Goksel; Karakadioglu, Gozde; Ozbeyli, Dilek; Ede, Seren; Yanardag, Refiye; Sacan, Ozlem; Aykac, AsliThis study was designed to investigate whether Petroselinum crispum (PC) extract has protective effects on the brain in the scopolamine-induced Alzheimer's disease (AD) rut model. The rats were divided into; control, scopolamine (1 mg/kg, i.p.), galantamine (1.5 mg/kg, i.p.) and PC extract (2 g/kg, p.o.)-treated scopolamine groups. On day 14, the novel object recognition test (NORT) and Morris water maze test (MWMT) were performed and then the rats were sacrificed. Scopolamine-induced cognitive impairments observed in the NORT and MWMT, significantly improved with PC extract and galantamine treatments. Scopolamine reduced M, receptor expression, Bcl-2/Bax ratio, and glutathione levels in the hippocampus and frontal cortex, while malondialdehyde levels, caspase-3/9 expressions, and acetylcholinesterase (AChE) activity were found to be increased. On the other band, PC and galantamine treatments reversed these changes. In conclusion, PC extract has shown an ameliorative effect on the spatial and recognition memory, M-1 receptor expression, apoptosis, oxidative stress, and increased AChE activity. Thus, it was concluded that PC could prevent AD-like conditions and can be used as a functional food. However, since animal models do not completely mimic those of humans, based on the data obtained in this study, the importance of PC on human AD should be demonstrated in future studies. (C) 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.Article Citation - WoS: 7Effect of Flurbiprofen Derivative (sgk597) on Cell Proliferation and Apoptosis of Breast Cancer Cell Lines(Istanbul Univ, Fac Pharmacy, 2022) Atlihan, Irem; Sevinc, Sevgi Kocyigit; Orun, Oya; Yilmaz, Ozgur; Kucukguzel, S. Guniz; Tiber, Pinar MegaBackground and Aims: The incidence of breast cancer is increasing day by day, especially in women. The search for new drugs against breast cancer is the focus of attention in research. Breast cancer and prostate cancer have remarkable biological similarities. Therefore, the 4-(4-chlorophenyl)-3-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-5-((4-fluorobenzyl)thio)-4H-1,2,4-triazole (SGK597) compound that is suppressing cell proliferation in prostate cancer, was studied in MCF-7 breast can-cer and MCF-10A mammary epithelial cell lines. Methods: The WST-8 method was used to determine cell viability and cytotoxicity of SGK597 in MCF-7 and MCF10-A cell lines. The JC-1 test was applied to determine changes in mitochondrial membrane potential. The protein expression levels of Bax, Bcl-2, and c-PARP associated with apoptosis were determined using Western blot analysis.Results: After 24 and 48 hours of incubation of SGK597, the IC50 values were 28.74 pM and 17.28 pM for MCF-7; 65.9 pM and 50.5 pM for MCF-10A, respectively. Mitochondrial membrane potential showed a tendency toward depolarization in MCF-7 cells as a result of increasing concentration of SGK597, while the same tendency was not seen for MCF-10A. As a result of western blot experiments, no increase in the Bax/Bcl-2 ratio and c-PARP expression level was observed, indicating no apoptosis.Conclusion: It was observed that the compound SGK597 suppressed MCF-7 cell proliferation. These results indicate that SGK597 may be a candidate compound for use as an anticancer agent. Keywords: Apoptosis, breast cancer, flurbiprofen, thioether, triazoleArticle 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.Article Citation - WoS: 41Citation - Scopus: 39Synthesis and Anticancer Activity of Novel Hydrazone Linkage-Based Aryl Sulfonate Derivatives as Apoptosis Inducers(Springer Birkhauser, 2022) Senkardes, Sevil; Han, M. Ihsan; Gurboga, Merve; Ozakpinar, Ozlem Bingol; Kucukguzel, S. Guniz; Güniz Küçükgüzel, Ş.; İhsan Han, M.In the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moieties were synthesized and characterized by FTIR, H-1-NMR, C-13-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC50 = 17.8 mu M and 21.2 mu M, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation. [GRAPHICS] .