Abstract
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.
| Original language | English |
|---|---|
| Article number | e0133656 |
| Journal | PloS one |
| Volume | 10 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2015 Jul 21 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
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Inhibition of ANO1/TMEM16A chloride channel by idebenone and its cytotoxicity to cancer cell lines. / Seo, Yohan; Park, Jinhong; Kim, Minseo; Lee, Ho K.; Kim, Jin Hee; Jeong, Jin Hyun; Namkung, Wan.
In: PloS one, Vol. 10, No. 7, e0133656, 21.07.2015.Research output: Contribution to journal › Article
TY - JOUR
T1 - Inhibition of ANO1/TMEM16A chloride channel by idebenone and its cytotoxicity to cancer cell lines
AU - Seo, Yohan
AU - Park, Jinhong
AU - Kim, Minseo
AU - Lee, Ho K.
AU - Kim, Jin Hee
AU - Jeong, Jin Hyun
AU - Namkung, Wan
PY - 2015/7/21
Y1 - 2015/7/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84941274386&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941274386&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0133656
DO - 10.1371/journal.pone.0133656
M3 - Article
C2 - 26196390
AN - SCOPUS:84941274386
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e0133656
ER -