New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer
Hua, Xiaohui1,2; Xua, Jiheng1; Deng, Xu3; Xu, Jiawei2; Li, Jingxia2; Zhu, David Q.2; Zhu, Junlan2; Jin, Honglei1; Tian, Zhongxian2; Huang, Haishan1; Zhao, Qin-shi3; Huang, Chuanshu1,2
2018
发表期刊CANCER LETTERS
ISSN0304-3835
卷号436页码:38-51
摘要ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone isolates that show potent anti-tumor potential in vivo and vitro. However, the anti-cancer activity and its potential mechanisms underlying ChlA-F action have never been explored. In the present study, we evaluated the potency of ChlA-F on autophagy-mediated anchorage-independent growth inhibition in human high-grade invasive bladder cancer (BC) cells. We found that ChlA-F treatment significantly inhibited anchorage-independent growth of human BC cells by inducing autophagy in a Sestrin-2 (SESN2)-dependent fashion. Our results revealed that ChlA-F treatment specifically induced SESN2 expression via increasing its transcription and mRNA stability. On one hand, ChlA-F treatment markedly attenuated Dicer protein abundance, in turn abolishing miR-27a maturation and further relieving miR-27a binding directly to SESN2 mRNA 3'UTR, thereby promoting SESN2 mRNA stabilization. On the other hand, ChlA-F treatment promoted Sp1 abundance and consequently mediated SESN2 transcription. These results demonstrate that its activation of the autophagic pathway through specifically promoting SESN2 expression mediates the anti-cancer effect of ChlA-F, which offers insights into the novel anti-cancer effect of ChlA-F on BC, as well as providing therapeutic alternatives against human BC.
关键词Anchorage-independent growth Cheliensisine A-fluoride (Ch1A-F) Macro-autophagy (autophagy) miR-27a Sestrin-2
资助信息NIH/NCI; NIH/NIEHS; Natural Science Foundation of China; Key Project of Science and Technology Innovation Team of Zhejiang Province
语种英语
资助项目NIH/NCI[CA217923] ; NIH/NCI[CA177665] ; NIH/NCI[CA165980] ; NIH/NIEHS[ES000260] ; Natural Science Foundation of China[NSFC91773391] ; Key Project of Science and Technology Innovation Team of Zhejiang Province[2013TD10]
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/62770
专题植物化学与西部植物资源持续利用国家重点实验室
通讯作者Zhao, Qin-shi; Huang, Chuanshu
作者单位1.Wenzhou Med Univ, Sch Life Sci, Zhejiang Prov Key Lab Technol & Applicat Model Or, Wenzhou, Zhejiang, Peoples R China
2.NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Yunnan, Peoples R China
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Hua, Xiaohui,Xua, Jiheng,Deng, Xu,et al. New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer[J]. CANCER LETTERS,2018,436:38-51.
APA Hua, Xiaohui.,Xua, Jiheng.,Deng, Xu.,Xu, Jiawei.,Li, Jingxia.,...&Huang, Chuanshu.(2018).New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer.CANCER LETTERS,436,38-51.
MLA Hua, Xiaohui,et al."New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer".CANCER LETTERS 436(2018):38-51.
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