Idebenone Inhibits Cell Proliferation by Blocking of ANO1/ TMEM16A Chloride Channel in Adenocarcinoma Cells
Poster Feb 11, 2015
Ca2+-activated Clˉ channels (CaCCs) play a pivotal role in a number of physiological processes including regulation of cell proliferation, differentiation and apoptosis. The expression levels of anoctamin 1 (ANO1, TMEM16A), a CaCC, are significantly increased in several tumors such as prostate adenocarcinomas and head and neck squamous cell carcinomas. Recent studies revealed that inhibition of ANO1 significantly reduced cell proliferation, cell migration, tumorigenesis and cancer progression. Here, we performed cell-based screening of a collection of drugs and drug-like compounds to identify inhibitors of ANO1. We found that idebenone, a synthetic analog of coenzyme Q10, is a potent inhibitor of ANO1. Electrophysiological studies showed that idebenone completely blocked ANO1 activity in ANO1 expressing FRT cells and significantly inhibited current of CaCC in PC-3 cells expressing abundant endogenous ANO1. Idebenone strongly inhibited cell migration in PC-3 cells, and it did not affect the intracellular Ca2+ concentration. We investigated the effect of idebenone on the cell proliferation and apoptosis in adenocarcinoma cell lines. Idebenone significantly reduced cell proliferation and induced apoptosis in PC-3, CFPAC-1, HT-29, T-84 and Calu-3 cells having CaCCs activities. These data suggest that idebenone, an ANO1/CaCC inhibitor, has potential for use in cancer therapy.
Multiplexing cell-based assays is possible using 3D culture models that are larger and more complex than monolayers
Real-time detection methods to measure live or dead cells provide much flexibility for multiplexing
All multiplexed assay combinations should be verified using appropriate controls for each 3D cell culture model.
Basic fibroblast growth factor (bFGF) is widely used in vitro for the maintenance and stimulation of a variety of cells. However, use of native bFGF in cell biology is limited by the fact that bFGF rapidly degrades at physiological temperatures. We have addressed this problem with an engineered form of bFGF, named Heat Stable bFGF (HS bFGF), which is stable at 37 degrees Celsius.READ MORE