title: Antroquinonol, a Ubiquinone Derivative from the Mushroom Antrodia camphorata, Inhibits Colon Cancer Stem Cell-like Properties: Insights into the Molecular Mechanism and Inhibitory Targets.
abstract: Antroquinonol (ANQ) is a ubiquinone derivative from the unique mushroom Antrodia camphorata, which exhibits broad-spectrum bioactivities. The effects of ANQ on cancer stem cell-like properties in colon cancer, however, remain unclear. In this study, we found that ANQ inhibited growth of colon cancer cells. The 50% growth inhibitions (GI50) of ANQ on HCT15 and LoVo were 34.8 ± 0.07 and 17.9 ± 0.07 μM. Moreover, ANQ exhibited inhibitory activities toward migration/invasion and tumorsphere formation of colon cancer cells. Mechanistically, ANQ inhibited pluripotent and cancer stem cell-related genes and down-regulated β-catenin/T-cell factor (TCF) signaling. Moreover, activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/β-catenin signaling axis was identified to be crucial for regulating the expressions of pluripotent genes, whereas suppression of PI3K/AKT by ANQ inhibited expressions of β-catenin and downstream targets. Molecular docking identified the potential interaction of ANQ with PI3K. Our data show for the first time that the bioactive component of A. camphorata, ANQ, suppresses stem cell-like properties via targeting PI3K/AKT/β-catenin signaling. ANQ could be a promising cancer prevention agent for colon cancer.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University , Taipei, Taiwan.
authors.forename: Hsien-Chun
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Pharmacy, College of Pharmacy, Taipei Medical University , Taipei, Taiwan.
authors.forename: Mei-Hsiang
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei, Taiwan.
authors.forename: Jiahn-Haur
authors.initials: JH
authors.lastname: Liao
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University , Taipei, Taiwan.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Wu
authors.affiliation: Institute of Fisheries Science, National Taiwan University , Taipei, Taiwan.
authors.forename: Tzong-Huei
authors.identifier: http://orcid.org/0000-0001-8036-7563
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei, Taiwan.
authors.forename: Fwu-Long
authors.initials: FL
authors.lastname: Mi
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University , Taipei, Taiwan.
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei, Taiwan.
authors.forename: Ku-Chung
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei, Taiwan.
authors.forename: Chia-Hsiung
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei, Taiwan.|TMU Center for Cell Therapy and Regeneration Medicine, Taipei Medical University , Taipei, Taiwan.
authors.forename: Cheng-Wei
authors.identifier: http://orcid.org/0000-0003-4622-2680
authors.initials: CW
authors.lastname: Lin
mesh_terms: D055491:Antrodia / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D062105:Molecular Docking Simulation; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051176:beta Catenin; D014451:Ubiquinone; C545357:antroquinonol; D019869:Phosphatidylinositol 3-Kinases
keywords: Antrodia camphorata; antroquinonol; cancer prevention; colon cancer stem cell; β-catenin