VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC
Zhou, Ling; Yi, Yuetao; Yuan, Qing; Zhang, Jing; Li, Youjie; Wang, Pingyu; Xu, Maolei; Xie, Shuyang
刊名FREE RADICAL BIOLOGY AND MEDICINE
2018-12
卷号129页码:177-185
关键词Vanadyl alginate oligosaccharides Non-small cell lung cancer ROS AKT PTEN
ISSN号0891-5849
DOI10.1016/j.freeradbiomed.2018.09.016
产权排序[Zhou, Ling ; Yuan, Qing ; Zhang, Jing ; Li, Youjie ; Wang, Pingyu ; Xie, Shuyang] Binzhou Med Univ, Dept Biochem & Mol Biol, Key Lab Tumor Mol Biol, Yantai 264003, Shandong, Peoples R China ; [Zhou, Ling ; Xu, Maolei] Binzhou Med Univ, Sch Pharm, Key Lab Tradit Chinese Med Prescript Effect & Cli, State Adm Tradit Chinese Med, Yantai 264003, Shandong, Peoples R China ; [Yi, Yuetao] Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai 264003, Peoples R China
文献子类Article
英文摘要Previous studies have confirmed that protein tyrosine phosphatase 1B (PTP1B) can promote tumour progression in non-small cell lung cancer (NSCLC). Vanadyl alginate oligosaccharides (VAOS) is a new coordination compounds that possesses a good PTP1B inhibitory activity. However, the potent anticancer efficacy of VAOS in human NSCLC requires further study. In this study, VAOS exhibited effective inhibitory effects in NSCLC both in cultured cells and in a xenograft mouse model. VAOS was further identified to induce NSCLC cell apoptosis through activating protein kinase B (AKT) to elevate intracellular reactive oxygen species (ROS) levels by increasing in oxygen consumption and impairing the ROS-scavenging system. Neither silencing of PTP1B by siRNA nor transient overexpression of PTP1B had an effect on the AKT phosphorylation triggered by VAOS, indicating that PTP1B inhibition was not involved in VAOS-induced apoptosis. Through phosphorus colorimetric assay, we demonstrated that VAOS notably inhibited phosphatase and tensin homologue deleted on chromosome 10 (PTEN) dephosphorylation activity, another member of the protein tyrosine phosphatases (PTPases)-upstream factor of AKT. Interestingly, PTEN knockdown sensitized cells to VAOS, whereas ectopic expression of PTEN markedly rescued VAOS-mediated lethality. In vivo, VAOS treatment markedly reduced PTEN activity and tumour cell burden with low systemic toxicity. Thus, our data not only provided a new therapeutic drug candidate for NSCLC, but presented new understanding into the pharmacological research of VAOS.
WOS关键词HEPATOCELLULAR-CARCINOMA ; OXIDATIVE STRESS ; PTEN ; CANCER ; CELLS ; MODULATION ; MECHANISMS ; SENESCENCE
WOS研究方向Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种英语
WOS记录号WOS:000450298400016
资助机构National Natural Science Foundation of China [81772281] ; Natural Science Foundation of Shandong Province [ZR2018BH046, ZR2018QH005] ; Project of Shandong Province Higher Educational Science and Technology Program [J15LM51] ; Taishan Scholar Project of Shandong Province [ts201712067]
内容类型期刊论文
源URL[http://ir.yic.ac.cn/handle/133337/24590]  
专题烟台海岸带研究所_海岸带生物学与生物资源利用所重点实验室
作者单位1.Binzhou Med Univ, Dept Biochem & Mol Biol, Key Lab Tumor Mol Biol, Yantai 264003, Shandong, Peoples R China;
2.Binzhou Med Univ, Sch Pharm, Key Lab Tradit Chinese Med Prescript Effect & Cli, State Adm Tradit Chinese Med, Yantai 264003, Shandong, Peoples R China;
3.Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai 264003, Peoples R China
推荐引用方式
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Zhou, Ling,Yi, Yuetao,Yuan, Qing,et al. VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC[J]. FREE RADICAL BIOLOGY AND MEDICINE,2018,129:177-185.
APA Zhou, Ling.,Yi, Yuetao.,Yuan, Qing.,Zhang, Jing.,Li, Youjie.,...&Xie, Shuyang.(2018).VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC.FREE RADICAL BIOLOGY AND MEDICINE,129,177-185.
MLA Zhou, Ling,et al."VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC".FREE RADICAL BIOLOGY AND MEDICINE 129(2018):177-185.
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