中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells

文献类型:期刊论文

作者Zhou, Hongyu1; Yu, Chunlei1,2; Kong, Lingmei1; Xu, Xiaoliang3; Yan, Juming1,4; Li, Yingchao3; An, Tao1,5; Gong, Liang1,4; Gong, Yaxiao1,4; Zhu, Huifang1,4
刊名ONCOGENE
出版日期2019-05-02
卷号38期号:18页码:3371-3386
ISSN号0950-9232
DOI10.1038/s41388-018-0674-5
通讯作者Zhang, Hongbin(zhanghb@ynu.edu.cn) ; Yang, Xiaodong(xdyang@ynu.edu.cn) ; Li, Yan(liyanb@mail.kib.ac.cn)
英文摘要Cancer stem cells (CSCs) have been implicated in metastasis, relapse, and therapeutic resistance of cancer, so successful cancer therapy may therefore require the development of drugs against CSCs or combining anti-CSCs drugs with conventional therapies. The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently activated signaling pathways in human cancer, playing a central role in tumorigenesis as well as the maintenance of CSCs. Here, we designed and identified B591, a dihydrobenzofuran-imidazolium salt, as a novel specific pan-PI3K inhibitor with potent inhibitory activity against class I PI3K isoforms, which showed effective inhibition of cellular PI3K/mTOR signaling pathway and robust antitumor activity in a set of cancer cell lines. Notably, compared with bulk tumor cell populations, B591 exhibited more potency in suppressing CSCs survival and inducing CSCs apoptosis, and presence of B591 effectively eliminated paclitaxel-enriched CSCs. B591 diminished self-renewal capacity and decreased the expression of epithelial-mesenchymal transition (EMT) markers of CSCs. In vivo, B591 preferentially decreased CSCs levels in mouse xenograft model of human breast cancer as evidenced especially by remarkable reduction of tumor-initiating ability. Consistent with the preferential targeting of CSCs, B591 effectively inhibited breast tumor metastasis and delayed tumor regrowth following paclitaxel treatment. Taken together, our findings establish B591, a novel PI3K inhibitor, as a strong candidate for clinical evaluation as a CSCs targeting agent.
WOS研究方向Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种英语
WOS记录号WOS:000466610000004
源URL[http://ir.kib.ac.cn/handle/151853/66774]  
专题昆明植物研究所_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Zhang, Hongbin; Yang, Xiaodong; Li, Yan
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
2.North Sichuan Med Coll, Sch Pharm, Inst Mat Med, Nanchong, Peoples R China
3.Yunnan Univ, Sch Chem Sci & Technol, Minist Educ & Yunnan Prov, Key Lab Med Chem Nat Resource, Kunming, Yunnan, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, Yunnan Key Lab Nat Med Chem, Kunming, Yunnan, Peoples R China
推荐引用方式
GB/T 7714
Zhou, Hongyu,Yu, Chunlei,Kong, Lingmei,et al. B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells[J]. ONCOGENE,2019,38(18):3371-3386.
APA Zhou, Hongyu.,Yu, Chunlei.,Kong, Lingmei.,Xu, Xiaoliang.,Yan, Juming.,...&Li, Yan.(2019).B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells.ONCOGENE,38(18),3371-3386.
MLA Zhou, Hongyu,et al."B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells".ONCOGENE 38.18(2019):3371-3386.

入库方式: OAI收割

来源:昆明植物研究所

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