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Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells

Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myelo...

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Autores principales: Shi, Huan, Li, Xin-Yu, Chen, Yao, Zhang, Xing, Wu, Yong, Wang, Zi-Xuan, Chen, Pan-Hong, Dai, Hui-Qi, Feng, Ji, Chatterjee, Sayantan, Li, Zhong-Jie, Huang, Xiao-Wei, Wei, Hong-Qiao, Wang, Jigang, Lu, Guo-Dong, Zhou, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758733/
https://www.ncbi.nlm.nih.gov/pubmed/33362534
http://dx.doi.org/10.3389/fphar.2020.534171
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author Shi, Huan
Li, Xin-Yu
Chen, Yao
Zhang, Xing
Wu, Yong
Wang, Zi-Xuan
Chen, Pan-Hong
Dai, Hui-Qi
Feng, Ji
Chatterjee, Sayantan
Li, Zhong-Jie
Huang, Xiao-Wei
Wei, Hong-Qiao
Wang, Jigang
Lu, Guo-Dong
Zhou, Jing
author_facet Shi, Huan
Li, Xin-Yu
Chen, Yao
Zhang, Xing
Wu, Yong
Wang, Zi-Xuan
Chen, Pan-Hong
Dai, Hui-Qi
Feng, Ji
Chatterjee, Sayantan
Li, Zhong-Jie
Huang, Xiao-Wei
Wei, Hong-Qiao
Wang, Jigang
Lu, Guo-Dong
Zhou, Jing
author_sort Shi, Huan
collection PubMed
description Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells.
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spelling pubmed-77587332020-12-25 Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells Shi, Huan Li, Xin-Yu Chen, Yao Zhang, Xing Wu, Yong Wang, Zi-Xuan Chen, Pan-Hong Dai, Hui-Qi Feng, Ji Chatterjee, Sayantan Li, Zhong-Jie Huang, Xiao-Wei Wei, Hong-Qiao Wang, Jigang Lu, Guo-Dong Zhou, Jing Front Pharmacol Pharmacology Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells. Frontiers Media S.A. 2020-12-10 /pmc/articles/PMC7758733/ /pubmed/33362534 http://dx.doi.org/10.3389/fphar.2020.534171 Text en Copyright © 2020 Shi, Li, Chen, Zhang, Wu, Wang, Chen, Dai, Feng, Chatterjee, Li, Huang, Wei, Wang, Lu and Zhou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Shi, Huan
Li, Xin-Yu
Chen, Yao
Zhang, Xing
Wu, Yong
Wang, Zi-Xuan
Chen, Pan-Hong
Dai, Hui-Qi
Feng, Ji
Chatterjee, Sayantan
Li, Zhong-Jie
Huang, Xiao-Wei
Wei, Hong-Qiao
Wang, Jigang
Lu, Guo-Dong
Zhou, Jing
Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
title Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
title_full Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
title_fullStr Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
title_full_unstemmed Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
title_short Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells
title_sort quercetin induces apoptosis via downregulation of vascular endothelial growth factor/akt signaling pathway in acute myeloid leukemia cells
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758733/
https://www.ncbi.nlm.nih.gov/pubmed/33362534
http://dx.doi.org/10.3389/fphar.2020.534171
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