Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition

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	Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition
其他题名	Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition
	Lv Wenwen; Qin Sining; Chen Congqin; Zhang Jinjie; Ren Tianshu; Xu Yongnan; Zhao Qingchun
	2014
发表期刊	ACTA PHARMACOLOGICA SINICA
ISSN	1671-4083
卷号	35 期号:5 页码:625-635
摘要	Aim: 2-(4,6-Dimethoxy-1,3-dioxoisoindolin-2-yl) ethyl 2-chloroacetate (QSN-10c) is one of isoindolone derivatives with antiproliferative activity against human umbilical vein endothelial cells (HUVECs). The aim of this study was to investigate its antitumor activity in vitro and anti-angiogenic effects in vitro and in vivo.
其他摘要	Aim: 2-(4,6-Dimethoxy-1,3-dioxoisoindolin-2-yl) ethyl 2-chloroacetate (QSN-10c) is one of isoindolone derivatives with antiproliferative activity against human umbilical vein endothelial cells (HUVECs). The aim of this study was to investigate its antitumor activity in vitro and anti-angiogenic effects in vitro and in vivo. Methods: K562 leukemic cells and HUVECs were used for in vitro studies. Cell viability was examined using MTT assay. Cell apoptosis and mitochondrial transmembrane potential (Δψm) were detected with flow cytometry. Tube formation and migration of HUVECs were studied using two-dimensional Matrigel assay and wound-healing migration assay, respectively. VEGF levels were analyzed with RT-PCR and Western blotting. A zebrafish embryo model was used for in vivo anti-angiogenic studies. The molecular mechanisms for apoptosis in K562 cells and antiangiogenesis were measured with Western blotting. Results: In antitumor activity studies, QSN-10c suppressed the viability of K562 cells and induced apoptosis in dose- and timedependent manners. Furthermore, QSN-10c dose-dependently decreased the Δψm in K562 cells, increased the release of cytochrome c and the level of Bax, and decreased the level of Bcl-2, suggesting that QSN-10c-induced apoptosis of K562 cells was mediated via the mitochondrial apoptotic pathway. In anti-angiogenic activity studies, QSN-10c suppressed the viability of HUVECs and induced apoptosis in dose dependent manners. QSN-10c treatment did not alter the Δψm in HUVECs, but dose-dependently inhibited the expression of VEGF, inhibited the tube formation and cell migration in vitro, and significantly suppressed the number of ISVs in zebrafish embryos in vivo. Furthermore, QSN-10c dose-dependently suppressed the phosphorylation of AKT and GSK3β in both HUVECs and K562 cells. Conclusion: QSN-10c is a novel antitumor compound that exerts both antitumor and anti-angiogenic effects via inhibiting the PI3K/ AKT/GSK3β signaling pathway.
关键词	ENDOTHELIAL GROWTH-FACTOR DRUG-INDUCED APOPTOSIS HEMATOLOGICAL MALIGNANCIES ACTIN REORGANIZATION ANTICANCER DRUG BONE-MARROW KINASE AKT CANCER THALIDOMIDE MIGRATION isoindolone anticancer drug leukemia zebrafish angiogenesis apoptosis AKT GSK3 beta
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:5142653
引用统计	被引频次：2[CSCD] [CSCD记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/148133
专题	中国科学院金属研究所
作者单位	中国科学院金属研究所
推荐引用方式 GB/T 7714	Lv Wenwen,Qin Sining,Chen Congqin,et al. Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition[J]. ACTA PHARMACOLOGICA SINICA,2014,35(5):625-635.
APA	Lv Wenwen.,Qin Sining.,Chen Congqin.,Zhang Jinjie.,Ren Tianshu.,...&Zhao Qingchun.(2014).Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition.ACTA PHARMACOLOGICA SINICA,35(5),625-635.
MLA	Lv Wenwen,et al."Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition".ACTA PHARMACOLOGICA SINICA 35.5(2014):625-635.