title: Inhibition of calcium-activated chloride channel ANO1 suppresses proliferation and induces apoptosis of epithelium originated cancer cells.
abstract: ANO1, a calcium-activated chloride channel, has been reported to be amplified or overexpressed in tissues of several cancers. However, reports on its roles in tumor progression obtained from cancer cell lines are inconsistent, suggesting that the role of ANO1 in tumorigenesis is likely dependent on either its expression level or cell-type expressing ANO1. To investigate the biological roles of ANO1 in different tumor cells, we, in this study, selected several cancer cell lines and a normal HaCaT cell line with high expression levels of ANO1, and examined the function of ANO1 in these cells using approaches of lentiviral knockdown and pharmacological inhibition. We found that ANO1 knockdown significantly inhibited cell proliferation and induced cell apoptosis in either tumor cell lines or normal HaCaT cell line. Moreover, silencing ANO1 arrested cancer cells at G1 phase of cell cycle. Treatment with ANO1 inhibitor CaCCinh-A01 reduced cell viability in a dose-dependent manner. Furthermore, both ANO1 inhibitors CaCCinh-A01 and T16Ainh-A01 significantly suppressed cell migration. Our findings show that ANO1 overexpression promotes cancer cell proliferation and migration; and genetic or pharmacological inhibition of ANO1 induces apoptosis and cell cycle arrest at G1 phase in different types of epithelium-originated cancer cells.
authors.affiliation: Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Lizhao
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao 266021, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.|Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao 266021, China.
authors.forename: KeWei
authors.initials: K
authors.lastname: Wang
mesh_terms: D000075369:Anoctamin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
chemical_list: C000607369:6-t-butyl-2-(furan-2-carboxamido)-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid; C476213:ANO1 protein, human; D000075369:Anoctamin-1; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011743:Pyrimidines; C578466:T16AInh-A01; D013844:Thiazoles; D013876:Thiophenes
keywords: ANO1; CaCCinh-A01; T16Ainh-A01; apoptosis; cancer; migration; proliferation