Astaxanthin (ASTX), a carotenoid with potent antioxidant properties, exists naturally in various plants, algae, and seafoods. In this study, we investigated the in vitro ability of ASTX to protect porcine lens crystallins from oxidative damage by iron-mediated hydroxyl radicals or by calcium ion-activated protease (calpain), in addition to the possible underlying biochemical mechanisms. ASTX (1 mM) was capable of protecting lens crystallins from being oxidized, as measured by changes in tryptophan fluorescence, in the presence of a Fenton reaction solution containing 0.2 mM Fe2+ and 2 mM H2O2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that beta(high)-crystallin was the most vulnerable protein under these conditions of free radical exposure. The proteolysis of lens crystallins induced by calcium ion-activated calpain was also inhibited by ASTX (0.03-1 mM) as determined by daily measurement of the light-scattering intensity at 405 nm for five consecutive days. ASTX at 1 mM was as potent as a concentration of 0.1 mM calpain inhibitor E64 in protecting the oxidative damage/hydrolysis of porcine crystallins. At a concentration of 1 mM, ASTX provided better protection than the endogenous antioxidant glutathione in terms of suppressing calcium-induced turbidity of lens proteins. Thin-layer chromatography analysis indicated that ASTX interacted with calcium ions to form complexes, which we believe interfere with the hydrolysis of lens crystallins by calcium-activated calpain. This in vitro study shows that ASTX is capable of protecting porcine lens proteins from oxidative insults and degradation by calcium-induced calpain.

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.

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Selenite, the most commonly encountered toxic form of selenium, in overdose, is used to induce cataracts in rats. This study demonstrated that selenite, but not selenate, would interact with the carotenoid astaxanthin (ASTX), as determined using isothermal titration calorimetry and NMR. The maximum absorption of ASTX decreased with increasing selenite concentration, indicating that the conjugated system of ASTX was changed by selenite. Such interactions between ASTX and selenite were also supported by the attenuation of selenite-induced turbidity by ASTX (0-12.5 microM) in vitro. In vivo experiments also showed that ASTX attenuated selenite-induced cataractogenesis in rats. In summary, this is the first report of a direct interaction of ASTX with selenite. This interaction is supported by an in vitro assay and may be partially responsible for the ASTX observed in vivo protection against selenite-induced cataractogenesis.