| B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells | |
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; Zhang, Hongbin3; Yang, Xiaodong3; Li, Yan1,5
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| 通讯作者 | Zhang, Hongbin(zhanghb@ynu.edu.cn) ; Yang, Xiaodong(xdyang@ynu.edu.cn) ; Li, Yan(liyanb@mail.kib.ac.cn) |
| 2019-05-02 | |
| 发表期刊 | ONCOGENE
 |
| ISSN | 0950-9232 |
| 卷号 | 38期号:18页码:3371-3386 |
| 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. |
| DOI | 10.1038/s41388-018-0674-5 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000466610000004 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/66775 |
| 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 | 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. |
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