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- Title
Gene Expression Profiling and Protein Analysis Reveal Suppression of the C-Myc Oncogene and Inhibition JAK/STAT and PI3K/AKT/mTOR Signaling by Thymoquinone in Acute Myeloid Leukemia Cells.
- Authors
Almajali, Belal; Johan, Muhammad Farid; Al-Wajeeh, Abdullah Saleh; Wan Taib, Wan Rohani; Ismail, Imilia; Alhawamdeh, Maysa; Al-Tawarah, Nafe M.; Ibrahim, Wisam Nabeel; Al-Rawashde, Futoon Abedrabbu; Al-Jamal, Hamid Ali Nagi
- Abstract
Overexpression of c-Myc plays an essential role in leukemogenesis and drug resistance, making c-Myc an attractive target for cancer therapy. However, targeting c-Myc directly is impossible, and c-Myc upstream regulator pathways could be targeted instead. This study investigated the effects of thymoquinone (TQ), a bioactive constituent in Nigella sativa, on the activation of upstream regulators of c-Myc: the JAK/STAT and PI3K/AKT/mTOR pathways in HL60 leukemia cells. Next-generation sequencing (NGS) was performed for gene expression profiling after TQ treatment. The expression of c-Myc and genes involved in JAK/STAT and PI3K/AKT/mTOR were validated by quantitative reverse transcription PCR (RT-qPCR). In addition, Jess assay analysis was performed to determine TQ's effects on JAK/STAT and PI3K/AKT signaling and c-Myc protein expression. The results showed 114 significant differentially expressed genes after TQ treatment (p < 0.002). DAVID analysis revealed that most of these genes' effect was on apoptosis and proliferation. There was downregulation of c-Myc, PI3K, AKT, mTOR, JAK2, STAT3, STAT5a, and STAT5b. Protein analysis showed that TQ also inhibited JAK/STAT and PI3K/AKT signaling, resulting in inhibition of c-Myc protein expression. In conclusion, the findings suggest that TQ potentially inhibits proliferation and induces apoptosis in HL60 leukemia cells by downregulation of c-Myc expression through inhibition of the JAK/STAT and PI3K/AKT signaling pathways.
- Subjects
GENE expression profiling; ACUTE myeloid leukemia; MYELOID cells; PROTEIN analysis; PROTEIN expression; PI3K/AKT pathway
- Publication
Pharmaceuticals (14248247), 2022, Vol 15, Issue 3, p307
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph15030307