Qadi Shahad A, Hassan Mohammed A, Sheikh Ryan A, Baothman Othman As, Zamzami Mazin A, Choudhry Hani, Al-Malki Abdulrahman Labeed, Albukhari Ashwag, Alhosin Mahmoud
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Basic Medical Sciences, College of Medicine and Health Sciences, Hadhramout University, Mukalla, Yemen.
Epigenet Insights. 2019 Apr 4;12:2516865719839011. doi: 10.1177/2516865719839011. eCollection 2019.
The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors involving various epigenetic readers and writers leading to enhanced cell proliferation and defective apoptosis. Thymoquinone (TQ), the major biologically active compound of black seed oil, has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effects on the epigenetic code of cancer cells are largely unknown. In the present study, we performed RNA sequencing to investigate the anticancer mechanisms of TQ-treated T-cell acute lymphoblastic leukemia cell line (Jurkat cells) and examined gene expression using different tools. We found that many key epigenetic players, including ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (, and , were downregulated in TQ-treated Jurkat cells. Interestingly, several TSGs, such as , and , known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated, along with the upregulation of several downstream pro-apoptotic genes, such as , and . Data obtained from RNA sequencing were confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in Jurkat cells, as well as in a human breast cancer cell line (MDA-MB-468 cells). We found that the decrease in cell proliferation and in the expression of , and genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose. Our results indicate that the use of TQ as an epigenetic drug represents a promising strategy for epigenetic therapy for both solid and blood tumors by targeting both DNA methylation and histone post-translational modifications.
肿瘤抑制基因（TSGs）的表观遗传沉默在多种实体瘤和血液肿瘤中普遍存在，涉及各种表观遗传识别蛋白和书写蛋白，导致细胞增殖增强和凋亡缺陷。黑种草油的主要生物活性化合物百里醌（TQ）通过靶向多种途径在各种肿瘤中显示出抗癌活性。然而，其对癌细胞表观遗传密码的影响在很大程度上尚不清楚。在本研究中，我们进行了RNA测序以研究TQ处理的T细胞急性淋巴细胞白血病细胞系（Jurkat细胞）的抗癌机制，并使用不同工具检测基因表达。我们发现，在TQ处理的Jurkat细胞中，许多关键的表观遗传因子，包括含泛素样植物同源结构域（PHD）和真核生物中有趣的新基因（RING）结构域1（ 和 ）被下调。有趣的是，一些已知在包括急性白血病在内的各种肿瘤中发生表观遗传沉默的TSGs，如 、 和 ，以及几个下游促凋亡基因，如 、 和 ，均上调。在Jurkat细胞以及人乳腺癌细胞系（MDA-MB-468细胞）中，使用定量逆转录聚合酶链反应（RT-qPCR）证实了从RNA测序获得的数据。我们发现，两种癌细胞系（Jurkat细胞和MDA-MB-468细胞）中细胞增殖的减少以及 、 和 基因表达的降低取决于TQ剂量。我们的结果表明，通过靶向DNA甲基化和组蛋白翻译后修饰，将TQ用作表观遗传药物代表了一种用于实体瘤和血液肿瘤表观遗传治疗的有前景的策略。
