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Abstract Title:

Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy.

Abstract Source:

Pharmacol Res. 2020 Feb 22:104721. Epub 2020 Feb 22. PMID: 32097750

Abstract Author(s):

Shuai Guo, Yafei Chen, Sai Shi, Xuzhao Wang, Hailin Zhang, Yong Zhan, Hailong An

Article Affiliation:

Shuai Guo

Abstract:

TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. In recently, it 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 ICof 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 lungadenocarcinoma treatment. Arctigenin can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.

Study Type : Animal Study, In Vitro Study
Additional Links
Pharmacological Actions : Antiproliferative : CK(4773) : AC(3450)

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