title: Inhibition of ANO1 by luteolin and its cytotoxicity in human prostate cancer PC-3 cells.
abstract: Anoctamin 1 (ANO1), a calcium-activated chloride channel, is highly amplified in prostate cancer, the most common form of cancer and leading causes of cancer death in men, and downregulation of ANO1 expression or its functional activity is known to inhibit cell proliferation, migration and invasion in prostate cancer cells. Here, we performed a cell-based screening for the identification of ANO1 inhibitors as potential anticancer therapeutic agents for prostate cancer. Screening of ~300 selected bioactive natural products revealed that luteolin is a novel potent inhibitor of ANO1. Electrophysiological studies indicated that luteolin potently inhibited ANO1 chloride channel activity in a dose-dependent manner with an IC50 value of 9.8 μM and luteolin did not alter intracellular calcium signaling in PC-3 prostate cancer cells. Luteolin inhibited cell proliferation and migration of PC-3 cells expressing high levels of ANO1 more potently than that of ANO1-deficient PC-3 cells. Notably, luteolin not only inhibited ANO1 channel activity, but also strongly decreased protein expression levels of ANO1. Our results suggest that downregulation of ANO1 by luteolin is a potential mechanism for the anticancer effect of luteolin.
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.|Department of Integrated OMICS for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul, Korea.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
authors.forename: Kunhi
authors.initials: K
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Park
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jeon
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Jo
authors.affiliation: Department of Integrated OMICS for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul, Korea.
authors.forename: Ho K
authors.initials: HK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.|Department of Integrated OMICS for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul, Korea.
authors.forename: Wan
authors.identifier: http://orcid.org/0000-0002-1480-7433
authors.initials: W
authors.lastname: Namkung
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D044949:Kaempferols / Q000494:pharmacology; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology
chemical_list: C476213:ANO1 protein, human; D000814:Aniline Compounds; D000075369:Anoctamin-1; D018118:Chloride Channels; C409648:Fluo 4; D044949:Kaempferols; D009363:Neoplasm Proteins; D014966:Xanthenes; C006552:kaempferol; D047311:Luteolin; D002118:Calcium