title: Repurposing the anti-malarial drug dihydroartemisinin suppresses metastasis of non-small-cell lung cancer via inhibiting NF-κB/GLUT1 axis.
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.
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Geng
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Xiuyi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Hanxiang
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Biobank, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Shen
authors.affiliation: Biobank, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.|Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Xiamen Diabetes Institution, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D051272:Glucose Transporter Type 1 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D051272:Glucose Transporter Type 1; D016328:NF-kappa B; C039060:artenimol
keywords: NF-κB; Warburg effect; dihydroartemisinin; metastasis; non-small-cell lung cancer