Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Has files: YesInstitution Author: search.filters.institutionAuthor.Güçlüler, Gözde

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  • Article
    Citation - WoS: 5
    Citation - Scopus: 7
    The Roles of Antiapoptotic Sphingosine Kinase-1 and Glucosylceramide Genes in Drug Induced Cell Death of Mcf-7 Breast Cancer Cells
    (Zerbinis Medical Publications, 2011) Güçlüler, Gözde; Pişkin, Özden; Baran, Yusuf
    Purpose: Sphingolipids are important signaling molecules mediating cell survival, proliferation, cell cycle regulation and apoptosis. Ceramide is the most vital sphingolipid which induces growth arrest, senescence, and apoptosis. In this study, we aimed to determine the roles of sphingosine kinase- 1 (SK-1) and glucosylceramide synthase (GCS) genes in paclitaxel, doxorubicin, tamoxifen, cyclophosphamide and docetaxel induced apoptosis in human MCF-7 breast cancer cells. Methods: IC50 values (drug concentration inhibiting cell growth by 50%) of the anticancer agents were calculated using XTT cell proliferation assay. Changes in mitochondrial membrane potential (MMP) were determined using JC-1 assay kit. Changes in the mRNA levels of SK-1 and GCS genes were measured by using RT-PCR technique. Results: The results demonstrated significant decrease in cellular proliferation and increase in loss of MMP in a dose-dependent manner. Paclitaxel, doxorubicin, tamoxifen, cyclophosphamide and docetaxel application downregulated SK-1 expression while paclitaxel, tamoxifen, cyclophosphamide and docetaxel but not doxorubicin downregulated GCS comparing to untreated control cells. Conclusion: These results show for the first time that these agents induce apoptosis in MCF-7 cells by downregulating the antiapoptotic SK-1 and GCS genes that may result in accumulation of apoptotic ceramides. © 2011 Zerbinis Medical Publications.
  • Article
    Citation - WoS: 6
    Citation - Scopus: 6
    Docetaxel Enhances the Cytotoxic Effects of Imatinib on Philadelphia Positive Human Chronic Myeloid Leukemia Cells
    (Taylor and Francis Ltd., 2009) Güçlüler, Gözde; Baran, Yusuf
    Chronic myelogenous leukemia (CML) results from a translocation between chromosomes 9 and 22 which generates BCR/ABL fusion protein and characterized by uncontrolled proliferation of immature white blood cells. Imatinib, a molecularly targeting anticancer agent, is used widely for the treatment of CML and showed significant activity in chronic and accelerated phases but much less in blast crisis phase. The resistance to imatinib especially in blast crisis phase is recognized as a major problem in the treatment of CML patients. Docetaxel is shown to arrest cells in G2/M phase of the cell cycle which makes cells more sensitive to chemo- and radiotherapy. In this study, we aimed to increase chemosensitivity of human K562 CML cells to imatinib in combination with docetaxel. Taken together, our results showed that the combination of imatinib and docetaxel decreased cellular proliferation and increased apoptosis in human K562 chronic myeloid leukemia cells as compared to any agent alone. Imatinib and docetaxel induced apoptosis through caspase-3 enzyme activity and mitochondrial membrane potential.