Al-Rawashde Futoon Abedrabbu, Al-Sanabra Ola M, Alqaraleh Moath, Jaradat Ahmad Q, Al-Wajeeh Abdullah Saleh, Johan Muhammad Farid, Wan Taib Wan Rohani, Ismail Imilia, Al-Jamal Hamid Ali Nagi
Department of Anatomy and Histology, Faculty of Medicine, Mutah University, Al-Karak 61710, Jordan.
Department of Medical Laboratory Sciences, Faculty of Science, Al-Balqa Applied University, Al-Salt 19117, Jordan.
Pharmaceuticals (Basel). 2023 Jun 15;16(6):884. doi: 10.3390/ph16060884.
The epigenetic silencing of tumor suppressor genes (TSGs) is critical in the development of chronic myeloid leukemia (CML). functions as a TSG and negatively regulates JAK/STAT signaling. Enhancement of expression by demethylation provides molecular targets for the treatment of various cancers. Thymoquinone (TQ), a constituent of seeds, has shown anti-cancer activities in various cancers. However, TQs effect on methylation is not fully clear. Therefore, the aim of this study is to assess TQs ability to enhance the expression of through modifying DNA methylation in K562 CML cells. The activities of TQ on cell cycle progression and apoptosis were evaluated using a fluorometric-red cell cycle assay and Annexin V-FITC/PI, respectively. The methylation status of was studied by pyrosequencing analysis. The expression of , , , , , and was determined using RT-qPCR. The protein phosphorylation of STAT3, STAT5, and JAK2 was assessed using Jess Western analysis. TQ significantly downregulated the gene, gene, and gene and upregulated the gene and gene. This led to hypomethylation and restoration of expression, resulting in inhibition of JAK/STAT signaling, induction of apoptosis, and cell cycle arrest. The observed findings imply that TQ promotes apoptosis and cell cycle arrest in CML cells by inhibiting JAK/STAT signaling via restoration of the expression of JAK/STAT-negative regulator genes.
肿瘤抑制基因（TSGs）的表观遗传沉默在慢性粒细胞白血病（CML）的发展中至关重要。 作为一种肿瘤抑制基因，对JAK/STAT信号传导起负调节作用。通过去甲基化增强 表达为各种癌症的治疗提供了分子靶点。百里醌（TQ）是 种子的一种成分，已在多种癌症中显示出抗癌活性。然而，TQ对甲基化的影响尚不完全清楚。因此，本研究的目的是评估TQ通过修饰K562 CML细胞中的DNA甲基化来增强 表达的能力。分别使用荧光红细胞周期测定法和Annexin V-FITC/PI评估TQ对细胞周期进程和细胞凋亡的活性。通过焦磷酸测序分析研究 的甲基化状态。使用RT-qPCR测定 、 、 、 、 和 的表达。使用Jess Western分析评估STAT3、STAT5和JAK2的蛋白磷酸化。TQ显著下调 基因、 基因和 基因，并上调 基因和 基因。这导致 表达的去甲基化和恢复，从而抑制JAK/STAT信号传导，诱导细胞凋亡并使细胞周期停滞。观察到的结果表明，TQ通过恢复JAK/STAT负调节基因的表达来抑制JAK/STAT信号传导，从而促进CML细胞中的细胞凋亡和细胞周期停滞。
