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Thymoquinone Inhibits JAK/STAT and PI3K/Akt/ mTOR Signaling Pathways in MV4-11 and K562 Myeloid Leukemia Cells

Constitutive activation of Janus tyrosine kinase-signal transducer and activator of transcription (JAK/STAT) and Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways plays a crucial role in the development of acute myeloid leukemia (AML) and chronic myel...

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Main Authors: Futoon Abedrabbu Al-Rawashde (Author), Abdullah Saleh Al-wajeeh (Author), Mansoureh Nazari Vishkaei (Author), Hanan Kamel M. Saad (Author), Muhammad Farid Johan (Author), Wan Rohani Wan Taib (Author), Imilia Ismail (Author), Hamid Ali Nagi Al-Jamal (Author)
Format: Book
Published: MDPI AG, 2022-09-01T00:00:00Z.
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Summary:Constitutive activation of Janus tyrosine kinase-signal transducer and activator of transcription (JAK/STAT) and Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways plays a crucial role in the development of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Thymoquinone (TQ), one of the main constituents of <i>Nigella sativa</i>, has shown anti-cancer activities in several cancers. However, the inhibitory effect mechanism of TQ on leukemia has not been fully understood. Therefore, this study aimed to investigate the effect of TQ on JAK/STAT and PI3K/Akt/mTOR pathways in MV4-11 AML cells and K562 CML cells. <i>FLT3</i>-ITD positive MV4-11 cells and <i>BCR-ABL</i> positive K562 cells were treated with TQ. Cytotoxicity assay was assessed using WSTs-8 kit. The expression of the target genes was evaluated using RT-qPCR. The phosphorylation status and the levels of proteins involved in JAK/STAT and PI3K/Akt/mTOR pathways were investigated using Jess western analysis. TQ induced a dose and time dependent inhibition of K562 cells proliferation. TQ significantly downregulated <i>PI3K</i>, <i>Akt</i>, and <i>mTOR</i> and upregulated <i>PTEN</i> expression with a significant inhibition of JAK/STAT and PI3K/Akt/mTOR signaling. In conclusion, TQ reduces the expression of <i>PI3K</i>, <i>Akt</i>, and <i>mTOR</i> genes and enhances the expression of <i>PTEN</i> gene at the mRNA and protein levels. TQ also inhibits JAK/STAT and PI3K/Akt/mTOR pathways, and consequently inhibits proliferation of myeloid leukemia cells, suggesting that TQ has potential anti-leukemic effects on both AML and CML cells.
Item Description:10.3390/ph15091123
1424-8247

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