Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells.
Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells.
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DOI：
10.3389/fphar.2020.534171
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发表时间：
2020
影响因子：
5.6
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Shi H;Li XY;Chen Y;Zhang X;Wu Y;Wang ZX;Chen PH;Dai HQ;Feng J;Chatterjee S;Li ZJ;Huang XW;Wei HQ;Wang J;Lu GD;Zhou J
急性髓性白血病（AML）是一种侵袭性血液系统恶性肿瘤，其特征是未成熟和功能障碍的骨髓细胞高度增殖性积聚。槲皮素（Quercetin，Qu）是一种黄酮类化合物，对多种实体瘤具有抗癌作用，但其对急性髓系白血病的作用研究较少，其机制尚不清楚。本研究旨在探讨槲皮素诱导急性髓细胞白血病细胞死亡的特异性靶点及可能机制。首先，我们发现槲皮素以凋亡的形式诱导细胞死亡，这是半胱天冬酶依赖的。其次，我们发现槲皮素诱导的细胞凋亡依赖于线粒体膜电位（MMP）和Bcl-2蛋白的降低。通过定量化学蛋白质组学方法，我们观察到槲皮素处理后VEGFR 2和PI 3 K/Akt信号通路的下调。同时，细胞研究也发现VEGFR 2和PI 3 K/Akt信号通路参与槲皮素对线粒体和Bcl-2蛋白的作用。当PI 3 K/Akt信号被激活时，MMP的降低和细胞死亡可以被挽救，这表明VEGFR 2和PI 3 K/Akt作为上游调节剂发挥槲皮素诱导AML细胞凋亡的作用。总之，我们的研究结果提供了令人信服的证据，槲皮素诱导细胞死亡，通过下调VEGF/Akt信号通路和AML细胞中的细胞凋亡。
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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影响因子：
7.2
作者：
Liu, Y.;Gong, W.;Gao, Q. L.
通讯作者：
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DOI：
10.1007/s10495-016-1320-8
发表时间：
2017-02
期刊：
Apoptosis : an international journal on programmed cell death
影响因子：
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通讯作者：
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影响因子：
3.7
作者：
Pratheeshkumar P;Son YO;Budhraja A;Wang X;Ding S;Wang L;Hitron A;Lee JC;Kim D;Divya SP;Chen G;Zhang Z;Luo J;Shi X
通讯作者：
Shi X
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影响因子：
5.6
作者：
Yi Ji;Li Li;Yan-Xia Ma;Wen-Ting Li;Liu Li;Heng-Zhou Zhu;Mian-Hua Wu;Jin-Rong Zhou
通讯作者：
Jin-Rong Zhou
影响因子：
20.3
作者：
Madlambayan, Gerard J.;Meacham, Amy M.;Cogle, Christopher R.
通讯作者：
Cogle, Christopher R.