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Document Type |
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Thesis |
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Document Title |
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TARGETING EPIGENETIC CODE IN CANCER CELL BY THYMOQUINONE استهداف الشفرة اللاجينية في الخلية السرطانية باستخدام الثيموكوينون |
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Subject |
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Faculty of Sciences |
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Document Language |
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Arabic |
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Abstract |
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The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors. Demethylation of both DNA methylation and histone methylation mediated by DNA methyltransferase 1 (DNMT1) and histone methyltransferase such as G9a, respectively, as well as histone acetylation with subsequent reactivation of TSGs result in the inhibition of cell proliferation and metastasis and triggering cell apoptosis. Thymoquinone (TQ), the major biologically active compound of the black seed has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effect on cancer cell epigenetic code is largely unknown. The present study aimed to investigate the effect of TQ on the “epigenetic cancer signature” in the human breast cancer cell line (MDA-MB-468 cells) and the human acute lymphoblastic leukemia (Jurkat cells) and the related events. We found that TQ induces dose-dependent inhibition of the cellular proliferation and induction of apoptosis in both cancer cell lines. RNA sequencing showed that the epigenetic integrator Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1), the DNA methyltransferases: DNMT1 DNMT3A, DNMT3B as well as several histone deacetylases including HDAC1, 4 and 9 were down-regulated in TQ treated of Jurkat cells. Interestingly, several tumor suppressor genes such as p16INK4A, ST7, PPARG, and FOXO4 known to be epigenetically silenced in various tumors including leukemia were up-regulated along with the up-regulation of several downstream pro-apoptotic genes such as RASL11B, RASD1, GNG3, BAD, and BIK. Data obtained from RNA sequencing were confirmed using RT-qPCR in Jurkat cells and MDA-MB-468 cells. We found that TQ decreases the expression of UHRF1, DNMT1, G9a and HDAC1 genes in both cancer cell lines in a dose dependent manner. These results suggest that TQ could be used as epigenetic drug that target both DNA methylation and histone post-translational modifications which could be a promising strategy for the epigenetic therapy for both solid and blood tumors. |
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Supervisor |
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Dr. Mahmoud Alhosin |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1439 AH
2018 AD |
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Co-Supervisor |
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Dr. Ashwag Albukhari |
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Added Date |
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Tuesday, August 7, 2018 |
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Researchers
| شهد عبدالقادر قاضي | Qadi, Shahad Abdulqader | Researcher | Master | |
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