Person: GÜNAYDIN AKYILDIZ, AYŞENUR
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Publication Open Access Ivermectin Induces Oxidative Stress and DNA Damage in Breast Cancer Cells(2023-01-01) Güler E. M.; Günaydın Akyıldız A.; GÜNAYDIN AKYILDIZ, AYŞENURObjective: Breast cancer (BC) remains to be one of the most diagnosed cancer types among women around the world. Drug repurposing is suggested to be a convenient alternative for drug development in cancer treatment. Ivermectin, the antiparasitic agent produced by the bacterium Streptomyces avermitilis, is currently being examined thoroughly in oncology and has begun to be seen as a potential drug candidate for BC therapy. However, studies are limited, and the exact anti-tumorigenic mechanism is not yet clarified in breast cancer. Methods: For elucidating the molecular mechanisms of Ivermectin’s potential anticancer effects, we have examined its in vitro effects on BC cells in terms of cell viability, intracellular ROS levels, glutathione levels, mitochondrial membrane potential, apoptosis, and DNA damage. Results: Ivermectin induces apoptosis via oxidative stress and DNA damage in BC cells. Conclusion: The in vitro mechanistic studies of promising anticancer agents for repurposing are essential guides for drug developers. For this purpose, ivermectin should be further studied as a drug candidate for its potential in the treatment of breast cancer.Publication Metadata only Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation.(2023-02-21) Jannuzzi A. T.; Korkmaz N. S.; Gunaydin Akyildiz A.; Arslan Eseryel S.; Karademir Yilmaz B.; Alpertunga B.; GÜNAYDIN AKYILDIZ, AYŞENURPublication Open Access Emodin and aloe-emodin, two potential molecules in regulating cell migration of skin cells through the MAP kinase pathway and affecting Caenorhabditis elegans thermotolerance(2023-12-01) GÜNAYDIN AKYILDIZ, AYŞENUR; Yanikoglu R. S.; Gulec M.; ALİM TORAMAN, GÜLBAHAR ÖZGE; Kuran E. D.; Atasoy S.; Olgun A.; Topcu G.; TOPÇU, GÜLAÇTI; ATASOY, SEZEN; GÜNAYDIN AKYILDIZ, AYŞENUR; ALİM TORAMAN, GÜLBAHAR ÖZGE; YANIKOĞLU, RABİA SAREBackground: Emodin and aloe-emodin are two anthraquinones having positive effects in wound healing. However, their mechanism of action of wound healing is not fully understood. The MAP kinase family, which plays an active role in wound healing, is a well-characterized large family of serine/threonine kinases and regulates processes such as proliferation, oncogenesis, differentiation, and inflammation in the cell. The aim of this study is to comparatively elucidate the mechanisms of action of emodin and aloe-emodin, which are potential agents in wound healing. Methods: The mechanism of the effects of emodin and aloe-emodin on cell viability and cell migration was examined using the human skin fibroblast (CCD-1079Sk) cell line. The gene expression levels of the MAP kinases (JNK, P38, ERK) in the skin fibroblast cells along with a molecular docking study analyzing their interaction potential were evaluated. Furthermore, the molecules’ effects on the lifespan of Caenorhabditis elegans were studied. Results: Emodin and aloe-emodin inhibited the ATP content of the cells in a concentration dependent manner and accelerated cell migration at the lower concentrations while inhibiting cell migration in the higher concentration treatment groups. The expressions of JNK and P38 were upregulated at the low concentrations and downregulated at the higher concentrations. The molecular docking studies of the molecules gave high docking scores indicating their interaction potential with JNK and P38. C. elegans lifespan under heat stress was observed longer after 75 µM emodin and was significantly reduced after 150 µM aloe-emodin treatment. Conclusion: Aloe-emodin was found to be more potent on cell viability, cell migration, gene expression levels of the MAP kinases in healthy fibroblastic skin cells, and on the lifespan of C. elegans. This study reveals the functional effects and the biological factors that interact in the wound healing process of emodin and aloe-emodin, and give a possible treatment alternative to shorten the duration of wound care.Publication Metadata only The cyclin-dependent kinase inhibitor abemaciclib-induced hepatotoxicity: Insight on the molecular mechanisms in HepG2/THP-1 co-culture model(2024-01-01) BORAN T.; ZENGİN Ö. S.; Seker Z.; GÜNAYDIN AKYILDIZ A.; ÖZTAŞ E.; ÖZHAN G.; GÜNAYDIN AKYILDIZ, AYŞENURDrug-induced liver injury (DILI) is one of the widespread causes of liver injury and immune system plays important role. Abemaciclib (ABE) is a cyclin-dependent kinase inhibitor used as monotherapy or combination therapy in the treatment of breast cancer. Like other kinase inhibitors, the underlying mechanisms of ABE-induced hepatotoxicity are not completely known yet. In the current study, hepatotoxicity of ABE was evaluated with HepG2/THP-1 co-culture model which has been developed in recent years for the evaluation of DILI potential. Following ABE treatment, oxidative stress, mitochondrial damage, cytokine secretion levels, apoptotic/necrotic cell death were determined. According to our results, ROS production along with GSH depletion was observed in HepG2 cells after ABE treatment. ABE promoted secretion of pro-inflammatory mediators (TNF-α and MCP-1) and declined anti-inflammatory cytokine IL-10 release. Besides, NFKβ and JNK1 protein expression levels increased following ABE treatment. ABE enhanced intracellular calcium levels, induced early apoptotic and necrotic cell deaths in HepG2 cells. Furthermore, the changes in some mitochondrial parameters including a reducement in intracellular ATP levels and complex V activity; hyperpolarized mitochondrial membrane potential and enhanced mitochondrial ROS levels were observed, whereas mitochondrial mass did not show any differences after ABE treatments. Therefore, ABE-induced hepatotoxic effects is probably via oxidative stress, inflammatory response and necrotic cell death rather than direct mitochondrial toxicity. In conclusion; the study makes a significant contribution to strengthening the infrastructure we have on in vitro toxicity mechanism evaluations, which are the basis of preclinical toxicity studies.Publication Metadata only An evaluation of a hepatotoxicity risk induced by the microplastic polymethyl methacrylate (PMMA) using HepG2/THP-1 co-culture model(2024-04-01) Boran T.; Zengin Ö. S.; Şeker Z.; Günaydın Akyıldız A.; Kara M.; Öztaş E.; Özhan G.; ŞEKER, ZEHRA; GÜNAYDIN AKYILDIZ, AYŞENUR