2. Academic Validation
  3. Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy

Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy

  • Pharmacol Res. 2020 May;155:104721. doi: 10.1016/j.phrs.2020.104721.
Shuai Guo 1,  Yafei Chen 2,  Sai Shi 1,  Xuzhao Wang 1,  Hailin Zhang 3,  Yong Zhan 4,  Hailong An 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China.
  • 2 Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China.
  • 3 Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
  • 4 State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China. Electronic address: zhany@hebut.edu.cn.
  • 5 State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China. Electronic address: hailong_an@hebut.edu.cn.
PMID: 32097750 DOI: 10.1016/j.phrs.2020.104721
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.

Keywords

Arctigenin; Inhibitor; Lung adenocarcinoma; Molecular target; TMEM16A.

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