Discovery of indoline derivatives that inhibit esophageal squamous cell carcinoma growth by Noxa mediated apoptosis
Discovery of indoline derivatives that inhibit esophageal squamous cell carcinoma growth by Noxa mediated apoptosis
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发现通过 Noxa 介导的细胞凋亡抑制食管鳞状细胞癌生长的二氢吲哚衍生物
DOI：
10.1016/j.bioorg.2019.103190
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发表时间：
2019-11-01
影响因子：
5.1
通讯作者：
Hu, Tao
中科院分区：
文献类型：
--
作者：
Fu, Dong-Jun;Li, Miaomiao;Hu, Tao
合成了一系列新的吲哚啉衍生物，并对四种选定的癌细胞系（Hela，A549，HepG2和KYSE 30）的抗增殖活性进行了评价。其中，化合物20对食管癌细胞（Kyse 30、Kyse 450、Kyse 510和EC 109）显示出有效的抑制活性。在食管鳞状细胞癌（ESCC）细胞中的细胞机制研究阐明了化合物20在体外和体内抑制细胞生长，减少集落形成，将细胞周期阻滞在M期，并诱导ESCC中的Noxa依赖性凋亡。重要的是，化合物20被鉴定为新的Noxa介导的凋亡诱导剂。这些结果表明，化合物20可能是一种有前途的抗癌药物，具有进一步临床应用的潜力。
A series of novel indoline derivatives were synthesized and evaluated for antiproliferative activity against four selected cancer cell lines (Hela, A549, HepG2 and KYSE30). Among them, compound 20 displayed the potent inhibition activity against esophageal cancer cells (Kyse30, Kyse450, Kyse510 and EC109). Cellular mechanism studies in esophageal squamous cell carcinoma (ESCC) cells elucidated compound 20 inhibited cell growths in vitro and in vivo, reduced colony formation, arrested cell cycle at M phase, and induced Noxa-dependent apoptosis in ESCC. Importantly, compound 20 was identified as a novel Noxa mediated apoptosis inducer. These results suggested that compound 20 might be a promising anticancer agent with potential for development of further clinical applications.