{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:23:10Z","timestamp":1790922190840,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Grant Scheme of the Ministry of Education, Malaysia","award":["FRGS\/1\/2019\/SKK08\/UNISZA\/02\/3 (RR330)"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK08\/UNISZA\/02\/3 (RR330)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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 Nigella sativa, 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. FLT3-ITD positive MV4-11 cells and BCR-ABL 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 PI3K, Akt, and mTOR and upregulated PTEN expression with a significant inhibition of JAK\/STAT and PI3K\/Akt\/mTOR signaling. In conclusion, TQ reduces the expression of PI3K, Akt, and mTOR genes and enhances the expression of PTEN 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.<\/jats:p>","DOI":"10.3390\/ph15091123","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T07:05:56Z","timestamp":1662620756000},"page":"1123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Thymoquinone Inhibits JAK\/STAT and PI3K\/Akt\/ mTOR Signaling Pathways in MV4-11 and K562 Myeloid Leukemia Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-5679","authenticated-orcid":false,"given":"Futoon Abedrabbu","family":"Al-Rawashde","sequence":"first","affiliation":[{"name":"School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Terengganu 21300, Malaysia"},{"name":"Department of Anatomy and Histology, Faculty of Medicine, Mutah University, Al-Karak 61710, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2550-5641","authenticated-orcid":false,"given":"Abdullah Saleh","family":"Al-wajeeh","sequence":"additional","affiliation":[{"name":"Anti-Doping Lab Qatar, Doha P.O. Box 27775, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1466-9752","authenticated-orcid":false,"given":"Mansoureh Nazari","family":"Vishkaei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of 17 August 1945, Jakarta 14350, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan Kamel M.","family":"Saad","sequence":"additional","affiliation":[{"name":"School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Terengganu 21300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6344-0220","authenticated-orcid":false,"given":"Muhammad Farid","family":"Johan","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Rohani Wan","family":"Taib","sequence":"additional","affiliation":[{"name":"School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Terengganu 21300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-4006","authenticated-orcid":false,"given":"Imilia","family":"Ismail","sequence":"additional","affiliation":[{"name":"School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Terengganu 21300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-2729","authenticated-orcid":false,"given":"Hamid Ali Nagi","family":"Al-Jamal","sequence":"additional","affiliation":[{"name":"School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA), Terengganu 21300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a034819","DOI":"10.1101\/cshperspect.a034819","article-title":"Epidemiology and etiology of leukemia and lymphoma","volume":"10","author":"Bispo","year":"2020","journal-title":"Cold Spring Harb. 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