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    Erianin, a promising agent in the treatment of glioblastoma multiforme triggers apoptosis in U373 and A172 glioblastoma cells
    (Inst Bioloska Istrazivanja Sinisa Stankovic, 2022) Kocoglu, Sema Serter; Secme, Mucahit; Elmas, Levent
    Glioblastoma is an aggressive, common and deadly primary intracranial brain tumor in adults. The antitumor activity of erianin, a dibenzyl compound found in Dendrobium chrysotoxum Lindl. extract, has not been previously demonstrated in glioblastoma. We investigated the anticancer activity and underlying mechanisms of erianin in human U373 and A172 glioma cells. The effects of erianin on cell viability, apoptosis, migration and invasion were estimated by the XTT test, the reverse transcription-polymerase chain reaction (RT-PCR), annexin V staining assay protocol for apoptosis, wound healing assay, and Matrigel (R) invasion chamber, respectively. The effective amounts of erianin in U373 and A172 cells were 16 and 64 mu M at 48 h, respectively. Erianin also significantly induced apoptosis by inhibiting B-cell lymphoma 2 (Bcl-2), caspase-8, caspase-9 and tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD), and activation of caspase-3 and BH3 interacting domain death agonist (BID) gene expression. In addition, erianin significantly increased the number of apoptotic cells in U373 and A172 cells and significantly decreased invasion and migration in U373 and A172 cells. Taken together, our results suggest that erianin may be a new therapeutic anticancer drug component with a potent apoptotic effect and a potential for treating glioblastoma.
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    Monensin, an Antibiotic Isolated from Streptomyces Cinnamonensis, Regulates Human Neuroblastoma Cell Proliferation via the PI3K/AKT Signaling Pathway and Acts Synergistically with Rapamycin
    (Mdpi, 2023) Kocoglu, Sema Serter; Secme, Muecahit; Oy, Ceren; Korkusuz, Gozde; Elmas, Levent
    Neuroblastoma is the most common extracranial childhood tumor and accounts for approximately 15% of pediatric cancer-related deaths. Further studies are needed to identify potential therapeutic targets for neuroblastoma. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. No study has reported the effects of monensin on SH-SY5Y neuroblastoma cells by targeting the PI3K/AKT signaling pathway. The aim of this study was to investigate the antiproliferative effects of monensin alone and in combination with rapamycin in human SH-SY5Y neuroblastoma cells mediated by the PI3K/AKT signaling pathway. The effects of single and combination applications of monensin and rapamycin on SH-SY5Y cell proliferation were investigated by XTT, and their effects on the PI3K/AKT signaling pathway by RT-PCR, immunohistochemistry, immunofluorescence, and Western blotting. The combined effects of monensin and rapamycin on SH-SY5Y proliferation were most potent at 72 h (combination index < 1). The combination of monensin and rapamycin caused a significant decrease in the expression of P21RAS, AKT, and MAPK1 genes. Single and combined administrations of monensin and rapamycin caused a significant decrease in PI3K/AKT expression. Our results showed for the first time that monensin exerts an antiproliferative effect by targeting the PI3K/AKT signaling pathway in neuroblastoma cells. It is suggested that monensin and its combination with rapamycin may be an effective therapeutic candidate for treating neuroblastoma.