Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin.
Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin.
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DOI：
10.1186/1756-9966-31-48
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发表时间：
2012-05-20
期刊：
影响因子：
--
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Huang Y;Hu J;Zheng J;Li J;Wei T;Zheng Z;Chen Y
黄芩苷是黄芩中的一种黄酮类化合物，通过诱导细胞凋亡抑制人白血病和骨髓瘤细胞的生长。本研究旨在探讨黄芩苷对培养的伯基特淋巴瘤细胞的凋亡作用。使用MTT和集落形成试验测量生长速率，并且使用膜联蛋白V和DNA片段化试验定量细胞凋亡的诱导。使用Western印迹法检查观察到的生长抑制的潜在机制。黄芩苷处理CA 46 Burkitt淋巴瘤细胞48 h可显著降低细胞增殖率，IC 50值为10 μM。10 μM黄芩苷几乎完全抑制集落形成。CA 46细胞在黄芩苷处理后发生凋亡，表现为膜联蛋白V介导的细胞百分比增加，DNA片段化增加，以及细胞死亡的内在（线粒体）途径激活，其特征在于caspase-9、caspase-3和聚（ADP-核糖）聚合酶裂解形式的表达增加。此外，黄芩苷被发现下调抗凋亡和上调磷脂酰肌醇-3-激酶（PI 3 K）/丝氨酸/苏氨酸激酶（Akt）信号通路的凋亡成分。黄芩苷改变CA 46细胞中PI 3 K/Akt通路组分表达的浓度与抑制生长和诱导凋亡的浓度相当，支持了黄芩苷在这些细胞中观察到的生长抑制和凋亡诱导作用是通过下调该通路介导的假设。
Baicalin, a flavone present in Scutellaria baicalensis Georgi, inhibits the growth of human leukemia and myeloma cells through induction of apoptosis. The present study was undertaken to ascertain whether cultured Burkitt lymphoma cells undergo apoptosis when treated with baicalin. Growth rates were measured using MTT and colony formation assays, and induction of apoptosis was quantified using Annexin V and DNA fragmentation assays. Mechanisms underlying observed growth suppression were examined using Western blotting. Treatment of CA46 Burkitt lymphoma cells with baicalin for 48 h markedly decreased the rate of cell proliferation; an IC50 value of 10 μM was obtained. Colony formation was almost fully suppressed at 10 μM baicalin. CA46 cells underwent apoptosis in response to baicalin treatment as evidenced by an increase in the percentage of cells stainable with Annexin V, by increased DNA fragmentation, and by activation of the intrinsic (mitochondrial) pathway for cell death as characterized by increased expression of the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase. Additionally, baicalin was found to down-regulate anti-apoptotic and up-regulate apoptotic components of the phosphatidylinositide-3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway. The concentrations at which baicalin altered expression of components of the PI3K/Akt pathway in CA46 cells were comparable to those that suppressed growth and induced apoptosis, supporting the hypothesis that the observed growth-inhibitory and apoptosis-inducing actions of baicalin in these cells are mediated by down-regulation of this pathway.
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影响因子：
12.4
作者：
Uriarte, SM;Joshi-Barve, S;Barve, S
通讯作者：
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影响因子：
2.1
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11.4
作者：
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影响因子：
2.7
作者：
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通讯作者：
Koeffler, H. Phillip
影响因子：
3.8
作者：
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通讯作者：
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