期刊
JOURNAL OF CANCER
卷 12, 期 13, 页码 4075-4085出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.57054
关键词
Non-small cell lung cancer; Artemisinin derivatives; Ferroptosis; Apoptosis; Caner therapy
类别
资金
- National Natural Science Foundation of China [81872167, 81472496]
- Changsha Science and Technology Bureau of Hunan Province [KQ1801036]
Artemisinin derivatives such as artemisinin and dihydroartemisinin have shown anti-proliferative effects on non-small cell lung cancer (NSCLC) cells by inducing apoptosis and ferroptosis. These findings suggest the potential application of artemisinin derivatives as novel therapeutic drugs for NSCLC.
Non-small cell lung cancer (NSCLC) is one of the major cancer-related causes of morbidity and mortality worldwide. Despite the progress in lung cancer treatment, there is still an urgent need to discover novel therapeutic agents for NSCLC. Natural products represent a rich source of bioactive compounds. Through a natural compound library screening assay, we found that a group of anti-insect drugs had significant inhibitory effect on the proliferation of NSCLC cells. Among the anti-insect drugs, two derivatives of artemisinin, i.e., artesunate (ART) and dihydroartemisinin (DHA), a group of well-known anti-malarial drugs, have been shown to possess selective anti-cancer properties. Mechanistically, we found that ART and DHA induced apoptosis of A549 cells as evidenced by decreased protein level of VDAC and increased caspase 3 cleavage. Furthermore, cystine/glutamate transporter (xCT), a core negative regulator of ferroptosis, was downregulated by ART and DHA. The mRNA level of transferrin receptor (TFRC), a positive regulator of ferroptosis, was upregulated by ART and DHA. ART/DHA-induced apoptosis and ferroptosis in NSCLC cells were partly reversed by N-Acetyl-L-cysteine (NAC), a ROS scavenger, and ferrostatin-1, a ferroptosis inhibitor, respectively. These results suggest that artemisinin derivatives have anti-NSCLC activity through induction of ROS-dependent apoptosis/ferroptosis. Our findings provide the experimental basis for the potential application of artemisinin derivatives as a class of novel therapeutic drugs for NSCLC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据