Repurposing the anti-malarial drug dihydroartemisinin suppresses metastasis of non-small-cell lung cancer via inhibiting NF-κB/GLUT1 axis

// Jie Jiang 1 , Guojun Geng 1 , Xiuyi Yu 1 , Hongming Liu 1 , Jing Gao 1 , Hanxiang An 2 , Chengfu Cai 1 , Ning Li 1 , Dongyan Shen 3 , Xiaoqiang Wu 3 , Lisheng Zheng 4 , Yanjun Mi 1, 2 , Shuyu Yang 5 1 Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 2 Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 3 Biobank, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 4 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China 5 Xiamen Diabetes Institution, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Correspondence to: Shuyu Yang, email: yangshuyu2016@126.com Yanjun Mi, email: Myjgj_77@163.com Keywords: dihydroartemisinin, non-small-cell lung cancer, Warburg effect, metastasis, NF-κB Received: April 06, 2016 Accepted: November 02, 2016 Published: November 24, 2016 ABSTRACT Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells. DHA inhibited in vitro migration and invasion of NSCLC cells even in low concentration with little cytotoxicity. Additionally, low concentration DHA also inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates NF-κB signaling to inhibit the GLUT1 translocation. Blocking the NF-κB signaling largely abolishes the inhibitory effects of DHA on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown significantly decreased the inhibition of invasion, and migration by DHA. Our results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose metabolism via inhibiting NF-κB signaling pathway and DHA may deserve further investigation in NSCLC treatment.