Antroquinonol, a Ubiquinone Derivative from the Mushroom Antrodia camphorata, Inhibits Colon Cancer Stem Cell-like Properties: Insights into the Molecular Mechanism and Inhibitory Targets
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- 作者：Hsien-Chun Lin ; Mei-Hsiang Lin ; Jiahn-Haur Liao ; Tzu-Hua Wu ; Tzong-Huei LeeFwu-Long Mi ; Chi-Hao Wu ; Ku-Chung Chen ; Chia-Hsiung Cheng ; Cheng-Wei Lin
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2017
- 出版时间：January 11, 2017
- 年：2017
- 卷：65
- 期：1
- 页码：51-59
- 全文大小：736K
- ISSN：1520-5118
文摘
Antroquinonol (ANQ) is a ubiquinone derivative from the unique mushroom <i>Antrodia camphoratai>, 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 <i>A. camphoratai>, ANQ, suppresses stem cell-like properties via targeting PI3K/AKT/β-catenin signaling. ANQ could be a promising cancer prevention agent for colon cancer.