Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy

Publication date: Available online 22 February 2020Source: Pharmacological ResearchAuthor(s): Shuai Guo, Yafei Chen, Sai Shi, Xuzhao Wang, Hailin Zhang, Yong Zhan, Hailong AnAbstractTMEM16A 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 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.Graphical abstract

Source: Pharmacological Research - February 24, 2020 Category: Drugs & Pharmacology Source Type: research