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

2020 ◽  
Vol 11 ◽  
Author(s):  
Huan Shi ◽  
Xin-Yu Li ◽  
Yao Chen ◽  
Xing Zhang ◽  
Yong Wu ◽  
...  

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.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yudi Ari Adi ◽  
Fajar Adi-Kusumo ◽  
Lina Aryati ◽  
Mardiah S. Hardianti

Acute myeloid leukemia (AML) is a malignant hematopoietic disorder characterized by uncontrolled proliferation of immature myeloid cells. In the AML cases, the phosphoinositide 3-kinases (PI3K)/AKT signaling pathways are frequently activated and strongly contribute to proliferation and survival of these cells. In this paper, a mathematical model of the PI3K/AKT signaling pathways in AML is constructed to study the dynamics of the proteins in these pathways. The model is a 5-dimensional system of the first-order ODE which describes the interaction of the proteins in AML. The interactions between those components are assumed to follow biochemical reactions, which are modelled by Hill’s equation. From the numerical simulations, there are three potential components targets in PI3K/AKT pathways to therapy in the treatment of AML patient.


Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 3133-3140 ◽  
Author(s):  
K Bhalla ◽  
AM Ibrado ◽  
E Tourkina ◽  
C Tang ◽  
S Grant ◽  
...  

Abstract Mitoxantrone has been shown in vitro to exhibit a steep dose-response relationship with respect to the clonogenic survival of acute myeloid leukemia cells. In this report, we show that 1-hour exposure of human myeloid leukemia HL-60 and KG-1 cells to mitoxantrone concentrations ranging between 0.1 and 10.0 mumol/L induced internucleosomal DNA fragmentation of approximately 200-bp integer multiples, characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Mitoxantrone-mediated PCD was associated with a steep inhibition of the clonogenic survival of the leukemic cells. In addition, intracellularly, mitoxantrone-induced PCD was associated with a marked induction of c-jun and significant repression of c-myc and BCL-2 oncogenes. Pretreatment with the protein kinase C stimulator phorbol myristate acetate enhanced mitoxantrone-induced internucleosomal DNA fragmentation, whereas protein kinase C inhibitors staurosporine and H7 had no effect. These findings suggest that PCD is a potential mechanism underlying the steep dose-response relationship of mitoxantrone to the inhibition of clonogenic survival of acute myeloid leukemia cells.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e52143 ◽  
Author(s):  
Mahban Irandoust ◽  
Julian Alvarez Zarate ◽  
Isabelle Hubeek ◽  
Ellen M. van Beek ◽  
Karin Schornagel ◽  
...  

FEBS Journal ◽  
2019 ◽  
Vol 287 (8) ◽  
pp. 1645-1665
Author(s):  
Yuxin Du ◽  
Kening Li ◽  
Xiangeng Wang ◽  
Aman Chandra Kaushik ◽  
Muhammad Junaid ◽  
...  

Oncotarget ◽  
2015 ◽  
Vol 6 (25) ◽  
pp. 21557-21571 ◽  
Author(s):  
Weihua Zhou ◽  
Jie Xu ◽  
Elise Gelston ◽  
Xing Wu ◽  
Zhengzhi Zou ◽  
...  

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