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Browsing Tezler by Author "Adan, Aysun"

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    Master Thesis
    Resveratrol'ün FLT3+ Akut Miyeloid Lösemide Terapötik Potansiyeli ve Resveratrol Tarafından Tetiklenen Apoptozda Seramid Metabolizmasının Rolü
    (Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2021) Nur Şebnem, ERSÖZ; Ersöz, Nur Şebnem; Adan, Aysun
    Resveratrol'ün FLT3-ITD+ AML hücreleri üzerindeki büyüme engelleyici etkilerinin altında yatan mekanizmalar, seramid metabolizması hedeflenerek araştırıldı. Resveratrol, SK (sfingosin kinaz) inhibitörü (SKI II), GCS (glukosilseramid sentaz) inhibitörü (PDMP)'nin tek başına ve kombinasyon halinde MOLM-13 ve MV4-11 hücreleri üzerindeki antiproliferatif, apoptotik ve sitostatik etkileri sırasıyla MTT, akış sitometrik Annexin-V/PI boyama ve PI boyama ile araştırıldı. Resveratrol muamelesi sonucu kaspaz-3 ve PARP kesimleri, GCS ve SK-1 protein ifadeleri ve kombinasyon muameleleri sonucu PARP kesimi western blot ile kontrol edildi. Kombinasyon indeksleri CompuSyn yazılımı ile hesaplanmıştır. Resveratrol'ün tek başına ve SKI II ve PDMP ile kombinasyonları, aditif veya sinerjik etkilerle hücre proliferasyonunu baskılamış, apoptozu indüklemesi ve hücre döngüsü ilerlemesini durdurmuştur. Resveratrol, GCS ve SK-1 ifadesini baskılamış ve kaspaz-3 ve PARP kesimi yoluyla apoptozu indüklemiştir. Kombinasyon muameleleri PARP aktivasyonu yoluyla apoptozu indüklemiştir. Sonuç olarak, resveratrolün FLT3-ITD + AML hücrelerinde büyümeyi baskılayıcı etkisi, SK-1 ve GCS'ın inhibe edilmesi aracılığı ile olmuştur ve bu iki enzimin inhibisyonu resveratrolün aktivitesini arttırmıştır.
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    Master Thesis
    THE ROLE OF CERAMIDE METABOLISM IN APOPTOSIS TRIGGERED BY RESVERATROL AND THE THERAPEUTIC POTENTIAL OF RESVERATROL IN PH+ ACUTE LYMPHOBLASTIC LEUKEMIA
    (Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2019) Oğuz, Osman; Adan, Aysun
    The mechanisms underlying the growth inhibitory effect of resveratrol on Ph + ALL cells were investigated with regard to targeting of ceramide metabolism and changes in BCR-ABL expression. Growth inhibition and apoptotic effects of resveratrol, SK inhibitor (SKI II), GCS inhibitor (PDMP), SPT inhibitor (myriocin) and resveratrol-inhibitor combinations were investigated by MTT cell proliferation test, Annexin-V/PI staining, caspase-3, PARP expression and cytochrome c release by western blot, while cytostatic effect was investigated by flow cytometry. The effect of resveratrol, inhibitors and combinations on BCR-ABL protein expression was determined by western blot. The effect of resveratrol on SPT, SK-1/2, GCS protein expression was determined by western blot. In both cell lines resveratrol and resveratrol with SKI II and PDMP suppressed cell growth, triggered apoptosis and arrested the cell cycle at S phase. Resveratrol: myriocin combination showed cell-specific effects on cell growth and cell cycle, but triggered apoptosis in both cells. Resveratrol and combinations generally increased cytochrome-c release, caspase-3 cleavage and PARP cleavage, but cell-specific changes were also detected. Resveratrol decreased the expression of SK-1 / SK2 and GCS in both cells and increased SPT expression. While resveratrol, SKI II and PDMP decreased BCR-ABL expression and myriocin increased BCR-ABL expression. Resveratrol: SKI II and resveratrol: PDMP caused increases in BCR-ABL, while resveratrol: myriocin reduced BCR-ABL expression. As a result, resveratrol suppressed cell growth and triggered apoptosis on Ph + ALL by regulating ceramide metabolism and BCR-ABL expression.