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In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS

Year 2022, Volume: 23 Issue: 1, 53 - 63, 15.04.2022
https://doi.org/10.23902/trkjnat.999403

Abstract

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 real-time 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 µM. 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 µM, 15 µM, and 25 µM 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 µM. 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.

Supporting Institution

Aksaray üniversitesi

Project Number

2017-058

Thanks

This study was financed by Aksaray University Scientific Research Fund (grant number 2017-058). We are thankful to Aksaray University Scientific and Technological Application and Research Center for the use of the Molecular Biology and Metabolism Laboratory. I would like to thank Biotechnologist Mehmet KARATAŞ for his kind help in the determination of molecular docking study.

References

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Year 2022, Volume: 23 Issue: 1, 53 - 63, 15.04.2022
https://doi.org/10.23902/trkjnat.999403

Abstract

Bu çalışmada, insan akut miyeloid lösemisinde timokinonun sitotoksik, apoptotik ve otofajik etkilerinin araştırılması amaçlandı. Timokinonun sitotoksik etkileri 3-(4,5-dimetiltiyazol2-yl)-2,5-difeniltetrazolyum-bromür (MTT) testi ile belirlendi. B hücre lenfoma 2 ile ilişkili X proteini (Bax), B hücre lenfoma 2 (Bcl-2), kaspaz 3, rapamisinin memeli hedefi (mTOR), fosfatidilinositol-3-kinaz (PI3K) ve protein kinaz B (AKT) gen ekspresyon analizleri kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (qRT-PCR) ile yapıldı. Bax, Bcl-2, kaspaz 3, mTOR, AKT ve PI3K proteinlerinin aktif bölgesindeki timokinonun potansiyel bağlanmasını araştırmak için AutoDock Tools 4.2 yazılımı kullanıldı. Timokinon, HL-60 hücrelerinde (İnsan lösemi hücre hattı) 16.35 µM değerinde sitotoksik etkiye neden olmuştur. Uygulanan tüm dozlarda kontrole göre Bcl-2 ekspresyonu azalmıştır. 10 µM, 15 µM ve 25 µM timokinon ile tedavi edilen hücrelerde kontrole göre kaspaz 3 ekspresyon seviyesinde bir azalma tespit edildi. Timokinon, tüm dozlarda kontrole kıyasla mTOR ve PI3K ifadelerinde önemli bir azalmaya neden olurken, AKT 15 µM'lik bir dozda azaldı. Yerleştirme sonuçları, timokinonun apoptotik ve otofajik proteinlerin aktif bölge amino asitleri ile hidrofobik etkileşimler ve hidrojen bağı yoluyla etkileşime girdiğini belirtti. Bulgularımız, timokinonun HL-60 hücrelerinde PI3K/AKT/mTOR yolunu önleyerek otofajiyi uyarabildiğini ve akut miyeloid lösemi tedavisi için yeni bir hedef olabileceğini düşündürmektedir.

Project Number

2017-058

References

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There are 47 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Research Article/Araştırma Makalesi
Authors

Neslihan Tekin Karacaer 0000-0002-0091-6428

Project Number 2017-058
Publication Date April 15, 2022
Submission Date September 23, 2021
Acceptance Date January 5, 2022
Published in Issue Year 2022 Volume: 23 Issue: 1

Cite

APA Tekin Karacaer, N. (2022). In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS. Trakya University Journal of Natural Sciences, 23(1), 53-63. https://doi.org/10.23902/trkjnat.999403
AMA Tekin Karacaer N. In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS. Trakya Univ J Nat Sci. April 2022;23(1):53-63. doi:10.23902/trkjnat.999403
Chicago Tekin Karacaer, Neslihan. “In Vitro AND in Silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS”. Trakya University Journal of Natural Sciences 23, no. 1 (April 2022): 53-63. https://doi.org/10.23902/trkjnat.999403.
EndNote Tekin Karacaer N (April 1, 2022) In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS. Trakya University Journal of Natural Sciences 23 1 53–63.
IEEE N. Tekin Karacaer, “In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS”, Trakya Univ J Nat Sci, vol. 23, no. 1, pp. 53–63, 2022, doi: 10.23902/trkjnat.999403.
ISNAD Tekin Karacaer, Neslihan. “In Vitro AND in Silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS”. Trakya University Journal of Natural Sciences 23/1 (April 2022), 53-63. https://doi.org/10.23902/trkjnat.999403.
JAMA Tekin Karacaer N. In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS. Trakya Univ J Nat Sci. 2022;23:53–63.
MLA Tekin Karacaer, Neslihan. “In Vitro AND in Silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS”. Trakya University Journal of Natural Sciences, vol. 23, no. 1, 2022, pp. 53-63, doi:10.23902/trkjnat.999403.
Vancouver Tekin Karacaer N. In vitro AND in silico EVALUATION OF THYMOQUINONE AS POTENTIAL ANTICANCER AGENT IN HUMAN ACUTE MYELOID LEUKEMIA HL-60 CELLS. Trakya Univ J Nat Sci. 2022;23(1):53-6.

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