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通过使人类白血病U937细胞中的磷脂酰肌醇3-激酶/蛋白激酶B信号通路失活诱导凋亡的乔治亚根提取物。

Induction of Apoptosis Georgi Root Extract by Inactivation of the Phosphatidyl Inositol 3-kinase/Akt Signaling Pathway in Human Leukemia U937 Cells.

作者信息

Choi Eun Ok, Hwang Hye-Jin, Choi Yung Hyun

机构信息

Department of Biochemistry, Dong-Eui University College of Korean Medicine, Busan, Korea.

Anti-Aging Research Center, Dong-Eui University, Busan, Korea.

出版信息

J Cancer Prev. 2019 Mar;24(1):11-19. doi: 10.15430/JCP.2019.24.1.11. Epub 2019 Mar 30.

DOI:10.15430/JCP.2019.24.1.11
PMID:30993090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6453591/
Abstract

BACKGROUND

The roots of Georgi (Labiatae) have been widely used in traditional medicine for treatment of various diseases. In this study, we investigated the effects of ethanol extracts of roots (EESB) on the growth ofn human leukemia U937 cells.

METHODS

The effect of EESB on cell viability was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apoptosis was determined using 4,6-diamidino-2-phenyllindile staining and flow cytometry. The effects of EESB on the expression of regulatory proteins of apoptosis and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling were determined by Western blotting. Caspase activity and mitochondrial membrane potential (MMP) were measured using flow cytometric analysis.

RESULTS

EESB significantly inhibited the growth of U937 cells and induced apoptosis, which was associated with down-regulation of anti-apoptotic Bcl-2, up-regulation of pro-apoptotic Bax, the loss of MMP and activation of caspase-9 and -3. We also found that EESB enhanced the expression of death receptors (DRs) and their associated ligands and induced the activation of caspase-8 and truncation of Bid. In addition, EESB suppressed PI3K/Akt signaling and EESB-induced apoptosis and growth inhibition were further increased by inhibition of PI3K activity.

CONCLUSIONS

Our results indicated that the pro-apoptotic effect of EESB was mediated through the activation of DR-mediated intrinsic and mitochondria-mediated extrinsic apoptosis pathways and inhibition of the PI3K/Akt signaling in U937 cells.

摘要

背景

糙苏（唇形科）的根在传统医学中已被广泛用于治疗各种疾病。在本研究中，我们研究了糙苏根乙醇提取物（EESB）对人白血病U937细胞生长的影响。

方法

采用3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-四氮唑溴盐法检测EESB对细胞活力的影响。使用4,6-二脒基-2-苯基吲哚染色和流式细胞术测定细胞凋亡。通过蛋白质免疫印迹法检测EESB对凋亡调节蛋白和磷脂酰肌醇3-激酶（PI3K）/Akt信号通路表达的影响。使用流式细胞术分析测定半胱天冬酶活性和线粒体膜电位（MMP）。

结果

EESB显著抑制U937细胞的生长并诱导细胞凋亡，这与抗凋亡蛋白Bcl-2的下调、促凋亡蛋白Bax的上调、MMP的丧失以及半胱天冬酶-9和-3的激活有关。我们还发现EESB增强了死亡受体（DRs）及其相关配体的表达，并诱导了半胱天冬酶-8的激活和Bid的截断。此外，EESB抑制PI3K/Akt信号通路，并且通过抑制PI3K活性进一步增强了EESB诱导的细胞凋亡和生长抑制。

结论

我们的结果表明，EESB的促凋亡作用是通过激活DR介导的内源性和线粒体介导的外源性凋亡途径以及抑制U9时细胞中的PI3K/Akt信号通路来介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/8d769197e4c3/jcp-24-011f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/9025b72801aa/jcp-24-011f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/44ae9c56504e/jcp-24-011f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/227f9a8d7dc1/jcp-24-011f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/c384c42358c0/jcp-24-011f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/42b26c939180/jcp-24-011f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/beeea567958c/jcp-24-011f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/8d769197e4c3/jcp-24-011f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/9025b72801aa/jcp-24-011f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/44ae9c56504e/jcp-24-011f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/227f9a8d7dc1/jcp-24-011f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/c384c42358c0/jcp-24-011f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/42b26c939180/jcp-24-011f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/beeea567958c/jcp-24-011f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762a/6453591/8d769197e4c3/jcp-24-011f7.jpg

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