Targeting Cyclin Dependent Kinases by Thymoquinone against Chronic Myeloid Leukemia: Molecular Docking and Gene Expression Analysis
نویسندگان
1 Department of Medical Laboratory Sciences, Al-Ahliyya Amman University, Amman, Jordan
2 Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan
3 Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Balqa Applied University, Al-Salt 19117, Jordan
4 School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Kuala Nerus 21300, Terengganu, Malaysia
5 Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Balqa Applied University, Al-Salt 19117, Jordan
6 School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Kuala Nerus 21300, Terengganu, Malaysia
doi
10.26655/JMCHEMSCI.2024.11.4چکیده
Genetic alterations in the cell cycle-regulator genes lead to cell cycle dysregulation and is considered a main driver of chronic myeloid leukemia (CML). Screenings of natural phytochemicals for drug discovery are common in modern medical research to combat cancer. One of the main ingredients of Nigella sativa seeds, thymoquinone (TQ), has demonstrated anti-cancer properties. However, more research is needed to completely explain the mechanism behind TQ's antileukemia effects. The current study aims to assess the TQ potential to inhibit CDK protein activities and to alter the expressions of the cell cycle-regulator genes in K562 CML cells. The cells were exposed to TQ for 48 h and 72 h and RT-qPCR was performed to assess the cell cycle-regulator gene expression. In silico evaluation by molecular docking of TQ to CDKs proteins was analysed and free-binding energy calculations were used. A significant downregulated CDK1 and upregulated p53 and p21 expressions were induced by TQ incubation for 48 h. A significant downregulated cyclin A2, cyclin D1, cyclin E1, cyclin B1, CDK1, CDK2, CDK4, CDK6, and CDK7 and upregulated p53, p16, p18, p21, and p27 expressions were induced by TQ incubation for 72 h. TQ inhibited CDK1, CDK2, CDK4, CDK6, and CDK7 protein activities. These findings identify TQ as a multi-targeted CDK inhibitor that could be potentially used as a therapeutic candidate to inhibit CML.
