Inhibition of ANO1 by luteolin and its cytotoxicity in human prostate cancer PC-3 cells

• Published in: PloS one Vol. 12; no. 3; p. e0174935
• Main Authors: Seo, Yohan, Ryu, Kunhi, Park, Jinhong, Jeon, Dong-kyu, Jo, Sungwoo, Lee, Ho K., Namkung, Wan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.03.2017; Public Library of Science (PLoS)
• Subjects: Analysis; Aniline Compounds - pharmacology; Animals; Anoctamin-1; Anticancer properties; Biocompatibility; Biology and Life Sciences; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium chloride; Calcium signalling; Cancer screening; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Channel gating; Chloride channels (calcium-gated); Chloride Channels - antagonists & inhibitors; Chloride Channels - metabolism; Chloride ions; Cytotoxicity; Gene expression; Growth factors; Health aspects; Humans; Immunoblotting; Intracellular signalling; Ion channels; Kaempferols - pharmacology; Kinases; Luteolin - pharmacology; Male; Medicine and Health Sciences; Molecular biology; Natural products; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - metabolism; Patch-Clamp Techniques; Penicillin; Pharmaceutical sciences; Pharmacology; Pharmacy; Physical Sciences; Prostate cancer; Prostatic Neoplasms - metabolism; Rats; Real-Time Polymerase Chain Reaction; Rodents; Signal transduction; Studies; Toxicity; Wound Healing - drug effects; Xanthenes - pharmacology
• DOI: 10.1371/journal.pone.0174935
• ISSN: 1932-6203

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.