Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
J Cell Mol Med. 2018 Dec;22(12):6213-6227. doi: 10.1111/jcmm.13908. Epub 2018 Sep 25.
Deguelin, a natural rotenoid isolated from several plants, has been reported to exert anti-tumour effects in various cancers. However, the molecular mechanism of this regulation remains to be fully elucidated. Here, we found that deguelin inhibited the growth of non-small cell lung cancer (NSCLC) cells both in vitro and in vivo by downregulation of Bmi1 expression. Our data showed that Bmi1 is highly expressed in human NSCLC tissues and cell lines. Knockdown of Bmi1 significantly suppressed NSCLC cell proliferation and colony formation. Deguelin treatment attenuated the binding activity of Bmi1 to the Noxa promoter, thus resulting in Noxa transcription and apoptosis activation. Knockdown of Bmi1 promoted Noxa expression and enhanced deguelin-induced apoptosis, whereas overexpression of Bmi1 down-regulated Noxa protein level and deguelin-induced apoptosis. Overall, our study demonstrated a novel apoptotic mechanism for deguelin to exert its anti-tumour activity in NSCLC cells.
裂环烯醚萜类化合物 deguelin 是从多种植物中分离得到的天然倍半萜，已被报道具有多种抗癌作用。然而，其调控机制仍有待充分阐明。本研究发现，deguelin 通过下调 Bmi1 表达，在体外和体内均能抑制非小细胞肺癌（NSCLC）细胞的生长。研究数据显示，Bmi1 在人 NSCLC 组织和细胞系中高表达。Bmi1 敲低显著抑制 NSCLC 细胞增殖和集落形成。deguelin 处理可减弱 Bmi1 与 Noxa 启动子的结合活性，从而导致 Noxa 转录和凋亡激活。Bmi1 敲低促进 Noxa 表达并增强 deguelin 诱导的细胞凋亡，而过表达 Bmi1 则下调 Noxa 蛋白水平并抑制 deguelin 诱导的细胞凋亡。总之，本研究揭示了 deguelin 在 NSCLC 细胞中发挥抗肿瘤活性的一种新的凋亡机制。
