دورية أكاديمية
Inhibition of ANO1/TMEM16A Chloride Channel by Idebenone and Its Cytotoxicity to Cancer Cell Lines.
| العنوان: | Inhibition of ANO1/TMEM16A Chloride Channel by Idebenone and Its Cytotoxicity to Cancer Cell Lines. |
|---|---|
| المؤلفون: | Seo, Yohan1, Park, Jinhong1, Kim, Minseo2, Lee, Ho K.1, Kim, Jin-Hee2, Jeong, Jin-Hyun2, Namkung, Wan1,2 wnamkung@yonsei.ac.kr |
| المصدر: | PLoS ONE. 7/21/2015, Vol. 10 Issue 7, p1-15. 15p. |
| مصطلحات موضوعية: | *CHLORIDE channels, *CELL-mediated cytotoxicity, *CANCER cell culture, *ENZYME inhibitors, *CANCER cell proliferation, *CYCLIC-AMP-dependent protein kinase |
| مستخلص: | The expression levels of anoctamin 1 (ANO1, TMEM16A), a calcium-activated chloride channel (CaCC), are significantly increased in several tumors, and inhibition of ANO1 is known to reduce cell proliferation and migration. Here, we performed cell-based screening of a collection of natural products and drug-like compounds to identify inhibitors of ANO1. As a result of the screening, idebenone, miconazole and plumbagin were identified as novel ANO1 inhibitors. Electrophysiological studies showed that idebenone, a synthetic analog of coenzyme Q10, completely blocked ANO1 activity in FRT cells expressing ANO1 without any effect on intracellular calcium signaling and CFTR, a cAMP-regulated chloride channel. The CaCC activities in PC-3 and CFPAC-1 cells expressing abundant endogenous ANO1 were strongly blocked by idebenone. Idebenone inhibited cell proliferation and induced apoptosis in PC-3 and CFPAC-1 cells, but not in A549 cells, which do not express ANO1. These data suggest that idebenone, a novel ANO1 inhibitor, has potential for use in cancer therapy. [ABSTRACT FROM AUTHOR] |
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