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AuthorAlmajali, Belal
AuthorJohan, Muhammad Farid
AuthorAl-Wajeeh, Abdullah Saleh
AuthorWan Taib, Wan Rohani
AuthorIsmail, Imilia
AuthorAlhawamdeh, Maysa
AuthorAl-Tawarah, Nafe M.
AuthorIbrahim, Wisam Nabeel
AuthorAl-Rawashde, Futoon Abedrabbu
AuthorAl-Jamal, Hamid Ali Nagi
Available date2022-03-06T05:02:28Z
Publication Date2022-03-03
Publication NamePharmaceuticals
Identifierhttp://dx.doi.org/10.3390/ph15030307
CitationAlmajali, B.; Johan, M.F.; Al-Wajeeh, A.S.; Wan Taib, W.R.; Ismail, I.; Alhawamdeh, M.; Al-Tawarah, N.M.; Ibrahim, W.N.; Al-Rawashde, F.A.; Al-Jamal, H.A.N. 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. Pharmaceuticals 2022, 15, 307. https://doi.org/10.3390/ ph15030307
URIhttp://hdl.handle.net/10576/27609
AbstractOverexpression 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. Nextgeneration 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.
Languageen
PublisherMDPI
Subjectthymoquinone
leukemia
c-Myc
c-Myc
JAK/STAT
PI3K/AKT
signaling
apoptosis
TitleGene 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
TypeArticle
Issue Number3
Volume Number15
ESSN1424-8247
dc.accessType Open Access


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