Browsing by Author "Tuncyurekli, Merve"

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Evaluation of the Toxicity Potential of Exercise and Atorvastatin/Metformin Combination Therapy on Stz-Diabetic Rats
(Springer, 2025) Tuncyurekli, Merve; Tuluce, Yasin; Erciyas, Ferzan Lermioglu
Exercise is recommended for individuals with diabetes, and metformin and atorvastatin are commonly prescribed to diabetic patients. However, these two drugs have potential effects that may lead to toxicity in the skeletal muscle system. Therefore, the effects and potential interactions of combining these two drugs on skeletal muscle performance and structure were investigated in vivo in an experimental diabetes model. Male Wistar rats were divided into six groups: a sedentary control group (N) and five treatment groups-exercise (C), diabetes (D), diabetes with metformin (MET), diabetes with atorvastatin (ATO), and diabetes with metformin and atorvastatin (MET + ATO). In the diabetes model experimentally created with streptozotocin (STZ; 45 mg/kg, i.p.) and metformin (300 mg/kg/day), atorvastatin (10 mg/kg/day) was administered to drug groups by gavage during the 4-week study period. The rats were allowed to run (at moderate level) for 30 min, 5 days a week, on the treadmill. At the end of the study, blood samples and gastrocnemius muscle tissues of the rats were obtained under ketamine anesthesia (100 mg/kg; i.p). The effects of combining exercise and medication on skeletal muscle were assessed by examining the levels of significant biomarkers including PGC-1 alpha, UCP-3, and MyHCs, as well as analyzing oxidative stress/antioxidant capacity parameters in muscle tissue samples. Additionally, relevant biochemical indicators were determined in serum samples. The quantity and morphology of mitochondria in muscle tissue were assessed using transmission electron microscopy. It was observed in the study that some toxic effects associated with the use of drugs alone were reduced by combination therapy. It is thought that this study will contribute to the literature in the evaluation of the effects of drugs and their combined use in Type 1 diabetes under exercise conditions.
Investigation of Potential Anti-Metastatic Effect of Metformin and Caffeic Acid Combination Therapy in Breast Cancer Cell Line in In-Vitro Culture Model
(Humana Press inc, 2025) Yavuz, Halil; Tuluce, Yasin; Karakus, Fuat; Kostekci, Sedat; Tuncyurekli, Merve; Keles, Ahmet Yasin
The invasion and metastasis of cancer cells transform localized cancers into systemic and life-threatening diseases, posing one of the most significant challenges in cancer treatment. This study tested the hypothesis that combined treatment with Caffeic acid (CA) and metformin (MTF) could inhibit or reduce effective signaling pathways involved in the proliferation, survival, and metastasis of MCF-7 breast cancer cells. Anti-proliferation analysis determined the IC50 values for MTF (4.5 mM) and CA (163 mu M) after 72 h. Cell migration analysis showed that MTF and CA significantly inhibited MCF-7 cell migration by the 72nd hour, both alone and in combination, without affecting HME1 healthy cell migration from the 48th hour. Colony formation analysis revealed that CA completely inhibited colony formation in MCF-7 cells, while MTF reduced it by 19%. ELISA results indicated that neither CA nor MTF affected the levels of VEGF-A, E-cadherin, or TINAGL-1 proteins, which are involved in MCF-7 cell migration and invasion. However, MTF significantly reduced IL-1 beta protein levels, and CA significantly reduced IL-4 protein levels in MCF-7 cells. RT-qPCR results largely supported the ELISA findings. Overall, CA and MTF exhibited potential to inhibit MCF-7 cell apoptosis, migration, tumor microenvironment modulation, and metastasis.
Investigation the Immunotherapeutic Potential of Mir-4477a Targeting Pd-1/Pd-l1 in Breast Cancer Cell Line Using a Cd8+ Co-Culture Model
(Springer, 2025) Tuluce, Yasin; Kostekci, Sedat; Karakus, Fuat; Keles, Ahmet Yasin; Tuncyurekli, Merve
BackgroundIn the present study, we investigated the immunotherapeutic and anticancer activities of microRNA-4477a (miR-4477a) as a PD-L1 inhibitor in breast cancer cells (MCF-7).MethodsTo this end, a series of analytical procedures were conducted, including bioinformatic analysis, RT-PCR analysis, PD-L1 ELISA, in vitro co-culture analysis, cytotoxicity assays, cell migration assays, and colony formation assays, with the objective of determining the anticancer activity of the compound in question.ResultsThe results demonstrated that miR-4477a can bind to three distinct regions of PD-L1 mRNA with high scores (94%, 88% and 80%), effectively targeting and suppressing the crucial regulatory pathways of cancer cells. In vitro studies demonstrated that a 25 nM dose of miR-4477a caused relatively high cytotoxicity in the MCF-7 cell line, suppressed PD-L1 gene expression, and decreased sPD-L1 protein levels, strongly inhibited cell migration, and significantly reduced colony formation. The in vitro co-culture analysis revealed that cancer cells were unable to evade the surveillance and cytotoxic activity of T cells (CD8+) due to the blockade of PD-L1 expression by miR-4477a.ConclusionsIn conclusion, miRNA-4477a has the capacity to regulate immune responses in breast cancer cells and may therefore be a promising candidate for use in cancer immunotherapy as a therapeutic agent.