In vitro and in silico evaluation of thymoquinone as potential anticancer agent in human acute myeloid leukemia hl-60 cells
Yükleniyor...
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya University
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
This study aims to explore the cytotoxic, apoptotic and autophagic effects of thymoquinone on human acute myeloid leukemia. The cytotoxic effects of thymoquinone were determined with 3-(4, 5-dimethylthiazol-2-yl)-2 and 5-diphenyltetrazolium bromide (MTT) tests. B-cell lymphoma 2 associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase 3, mammalian target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) gene expression analyzes were studied with quantitative realtime polymerase chain reaction (qRT-PCR). AutoDock Tools 4.2 software was applied to research the potential binding of thymoquinone in the active sites of Bax, Bcl-2, caspase 3, mTOR, PI3K, and AKT proteins. Thymoquinone caused a cytotoxic effect on HL-60 cells (Human leukemia cell line) with a value of 16.35 mu M. Bcl-2 expression was decreased in all concentrations applied compared to the control. A decrease in caspase 3 expression level was detected in the cells treated with 10 mu M, 15 mu M, and 25 mu M thymoquinone compared to the control. Thymoquinone induced an important decrease in mTOR and PI3K expressions compared to the control at all doses, while AKT decreased at a dose of 15 mu M. The docking outcomes showed that thymoquinone interacts with the active site amino acids of apoptotic and autophagic proteins via hydrophobic interactions and hydrogen bonding. The present findings suggest that thymoquinone can stimulate autophagy by prevention of PI3K/AKT/mTOR pathway in HL-60 cells and may become a new target for the therapy of acute myeloid leukemia.
Açıklama
Anahtar Kelimeler
AML, Apoptosis, Autophagy, PI3K/AKT/mTOR, Thymoquinone, Molecular Docking
Kaynak
Trakya University Journal of Natural Sciences
WoS Q DeÄŸeri
N/A
Scopus Q DeÄŸeri
Cilt
23
Sayı
1
