Antroquinonol, a Ubiquinone Derivative from the Mushroom Antrodia camphorata, Inhibits Colon Cancer Stem Cell-like Properties: Insights into the Molecular Mechanism and Inhibitory Targets
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
65
Journal Issue
1
Pages
51 - 59
Date Issued
2017-01
Author(s)
Hsien-Chun Lin
Mei-Hsiang Lin
Jiahn-Haur Liao
Tzu-Hua Wu
Fwu-Long Mi
Chi-Hao Wu
Ku-Chung Chen
Chia-Hsiung Cheng
Cheng-Wei Lin
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 cellrelated 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. ?2016 American Chemical Society.
Subjects
Antrodia camphorata; Antroquinonol; Cancer prevention; Colon cancer stem cell; β-catenin
SDGs
Other Subjects
Diseases; Antrodia camphorata; Antroquinonol; Cancer prevention; Colon cancer; Molecular mechanism; Ubiquinone; Stem cells; antroquinonol; beta catenin; phosphatidylinositol 3 kinase; ubiquinone; analogs and derivatives; Antrodia; cancer stem cell; cell proliferation; chemistry; Colonic Neoplasms; cytology; drug effects; genetics; human; metabolism; molecular docking; pathophysiology; signal transduction; tumor cell line; Antrodia; beta Catenin; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Humans; Molecular Docking Simulation; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Signal Transduction; Ubiquinone
Type
journal article