Mechanism of natural product crocin in the treatment of lung adenocarcinoma targeting TMEM16A ion channel

Abstract

TMEM16A plays a vital role in various physiological activities in the human body, and it is a potential drug target for many diseases. Recently, several studies have shown that the high expression of TMEM16A in lung cancer is closely related to the proliferation and migration of lung cancer cells. This work demonstrates that crocin is a new natural-product inhibitor of TMEM16A and it can inhibit the proliferation and migration of lung cancer cells through TMEM16A. Our results showed that crocin inhibits TMEM16A whole-cell currents in a concentration-dependent manner with an IC 50 value of 38.32 ± 2.31 μM. CCK8 and wound healing studies showed that crocin inhibits the proliferation and migration of lung cancer cells LA795 and NCI-H1299 in a concentration-dependent manner; however, it does not affect the proliferation and migration of 2BS cells. In addition, the inhibitory effect of crocin on the proliferation and migration of LA795 cells can be overcome by knockdown of TMEM16A using shRNA. In conclusion, this work suggests that TMEM16A is a potential drug target of crocin as it can inhibit the proliferation and migration of lung cancer. Crocin can be further evaluated as an intriguing lead for lung cancer treatment.