Downregulation of ANO1 activity in PC‐9 cells modulated by a new novel candidate TMEMinh001

Abstract

Relevant to multiple studies, calcium activated chloride channel called Anoctamin1 (ANO1) is identified as an excellent biomarker for tumor growth reported in different cancer cells such as prostate, breast, and lung cancer. Growing evidence suggests, ANO1 promotes tumor growth via regulating EGFR signaling and modulating MAPK and protein kinase B pathway. In non‐small cell lung cancer (NSCLC), the ANO1 expression level is high, leading to high cancer‐related mortality. To date, several natural and synthetic compounds have shown their modulatory effect on ANO1 activity but are out of the limelight due to selectivity. Our present study is carried out based on finding a selective and potent modulator of ANO1 activity by in silico and in vitro assay. According to the hypothesis, inhibitors of ANO1 are screened out, where an inhibitor reduced ANO1 expression without modulating intracellular Ca+ level and cystic fibrosis transmembrane conductance regulator (CFTR) channel activity. The molecular docking study revealed negative high binding free energy than known inhibitor Ani9 and other candidate compounds. Furthermore, our potential compound suppressed cell viability and migration process in ANO1 expressing PC9 cells, while not in H1975 cells not expressing ANO1. Besides, it initiated the apoptosis process by up‐regulating caspase‐3 activity. Thus, the above results provided significant evidence of the anticancer effect of the final compound against ANO1, reducing its protein level in NSCLC.