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Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition
Alternative TitleIsoindolone 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
Source PublicationACTA PHARMACOLOGICA SINICA
ISSN1671-4083
Volume35Issue:5Pages:625-635
AbstractAim: 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.
Other AbstractAim: 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.
KeywordENDOTHELIAL 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
Indexed ByCSCD
Language英语
CSCD IDCSCD:5142653
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Document Type期刊论文
Identifierhttp://ir.imr.ac.cn/handle/321006/148131
Collection中国科学院金属研究所
Affiliation中国科学院金属研究所
Recommended Citation
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.
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