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 (GI) 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.

Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells

“…These results suggest that the cell survival benefits from autophagy, with implications for the long-term resolution of colorectal cancer (Kantara et al, 2014). Antroquinonol, isolation from mushroom Antrodia camphorata, triggered PI3K/Akt/β-catenin signaling and could be a favorable cancer prevention agent for colon CSCs (Lin et al, 2017). Bitter melon extracts, isolated from Momordica charantia, inhibit CCSCs by affecting energy homeostasis in addition to increase Beclin-1, Atg7 and 12 autophagic protein in HT-29, and SW480 colon cancer cells (Kwatra et al, 2013).…”

A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer

“…Recent studies have reported that Antroquinonol induces apoptosis and autophagy of pancreatic cancer cells [ 156 ]. In colon cancer, ANQ has been found to suppress stem cell-like properties by targeting PI3K/AKT/β-catenin signalling [ 157 ].…”

Enhancement of antroquinonol production during batch fermentation using pH control coupled with an oxygen vector

“…[17][18][19][20] Antroquinonol, a ubiquinone derivate that has been isolated from the solid-state fermentation mycelium of A. camphorata, 21 has been shown to have bioactive properties, such as anticancer and anti-inflammatory activity. [22][23][24][25][26][27][28] It is also reported that antroquinonol could lower brain amyloid-levels and improve spatial learning and memory in a transgenic mouse model of Alzheimer's disease. 29 Generally, antroquinonol cannot be biosynthesized in submerged fermentation.…”

“…Several bioactive compounds were isolated and identified from A. camphorata , such as terpenoids and polysaccharides . Antroquinonol, a ubiquinone derivate that has been isolated from the solid‐state fermentation mycelium of A. camphorata , has been shown to have bioactive properties, such as anticancer and anti‐inflammatory activity . It is also reported that antroquinonol could lower brain amyloid‐β levels and improve spatial learning and memory in a transgenic mouse model of Alzheimer's disease .…”