Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy. (May 2020)

• Record Type: Journal Article
• Authors: Guo, Shuai; Chen, Yafei; Shi, Sai; Wang, Xuzhao; Zhang, Hailin; Zhan, Yong; An, Hailong
• Is Part Of: Pharmacological research. Volume 155(2020)
• Publication Date: 2020-05
• Subjects: NSCLC non-small cell lung cancer -- FBS fetal bovine serum -- MTT 3-(4, 5-d, imethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide -- DMEM dimethyl sulfoxide -- CLSM confocal laser scanning microscopy -- LGA lamarckian genetic algorithm -- RMS root mean square -- MAPK mitogen-activated protein kinase; TMEM16A -- Inhibitor -- Arctigenin -- Lung adenocarcinoma -- Molecular target; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104721
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. Recently, TMEM16A has started to be regarded as potential primary lung adenocarcinoma targets. Here, we identified that arctigenin, a natural compound, is a novel TMEM16A inhibitor, and it can suppress lung adenocarcinoma growth through inhibiting TMEM16A both in vitro and in vivo . Our data also showed that the IC50 of actigenin to TMEM16A whole-cell current was 19.29 ± 4.69 μM, and the putative binding sites of arctigenin in TMEM16A were R515 and R535. Arctigenin concentration-dependently inhibited the proliferation and migration of LA795, however, the inhibition effect can be abolished by knockdown of the endogenous TMEM16A with shRNA. Further, we injected arctigenin on xenograft mouse model which exhibited significant antitumor activity with no adverse effect. At last, western blotting results showed the mechanism of arctigenin inhibiting lung adenocarcinoma was through inhibiting MAPK pathway. In summary, TMEM16A is a novel drug target for lung adenocarcinoma treatment. Arctigenin can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.