In vitro and in vivo anti-colon cancer effects of Garcinia mangostana xanthones extract.
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BACKGROUND: Xanthones are a group of oxygen-containing heterocyclic compounds with remarkable pharmacological effects such as anti-cancer, antioxidant, anti-inflammatory, and antimicrobial activities. METHODS: A xanthones extract (81% alpha-mangostin and 16% gamma-mangostin), was prepared by crystallization of a toluene extract of G. mangostana fruit rinds and was analyzed by LC-MS. Anti-colon cancer effect was investigated on HCT 116 human colorectal carcinoma cells including cytotoxicity, apoptosis, anti-tumorigenicity, and effect on cell signalling pathways. The in vivo anti-colon cancer activity was also investigated on subcutaneous tumors established in nude mice. RESULTS: The extract showed potent cytotoxicity (median inhibitory concentration 6.5 +/- 1.0 mug/ml), due to induction of the mitochondrial pathway of apoptosis. Three key steps in tumor metastasis including the cell migration, cell invasion and clonogenicity, were also inhibited. The extract and alpha-mangostin up-regulate the MAPK/ERK, c-Myc/Max, and p53 cell signalling pathways. The xanthones extract, when fed to nude mice, caused significant growth inhibition of the subcutaneous tumor of HCT 116 colorectal carcinoma cells. CONCLUSIONS: Our data suggest new mechanisms of action of alpha-mangostin and the G. mangostana xanthones, and suggest the xanthones extract of as a potential anti-colon cancer candidate. (+info)
Inhibition of human aldose reductase-like protein (AKR1B10) by alpha- and gamma-mangostins, major components of pericarps of mangosteen.
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A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, was recently identified as both diagnostic marker and therapeutic target in the treatment of several types of cancer. In this study, we have examined AKR1B10 inhibition by five xanthone derivatives, components of pericarps of mangosteen, of which alpha- and gamma-mangostins show potential anti-cancer properties. Among the five xanthones, gamma-mangostin was found to be the most potent competitive inhibitor (inhibition constant, 5.6 nM), but its 7-methoxy derivative, alpha-mangostin, was the second potent inhibitor (inhibition constant, 80 nM). Molecular docking of the two mangostins in AKR1B10 and site-directed mutagenesis of the putative binding residues revealed that Phe123, Trp220, Val301 and Gln303 are important for the tight binding of gamma-mangostin, and suggested that the 7-methoxy group of alpha-mangostin impairs the inhibitory potency by altering the orientation of the inhibitor molecule in the substrate-binding site of the enzyme. (+info)
alpha-Mangostin: anti-inflammatory activity and metabolism by human cells.
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Distribution of major xanthones in the pericarp, aril, and yellow gum of mangosteen (Garcinia mangostana linn.) fruit and their contribution to antioxidative activity.
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Xanthone compounds in mangosteen (Garcinia mangostana Linn.) fruit have been reported to have biological activities including antioxidative and anti-inflammatory effects, and the major xanthone compounds in mangosteen are alpha-mangostin and gamma-mangostin. The objectives of this research were to quantify and qualify the major xanthones in each part of the mangosteen fruit with and without yellow gum from the point of view of effective utilization of agricultural product. Quantitative evaluation revealed that yellow gum had extremely high amounts of alpha-mangostin and gamma-mangostin (382.2 and 144.9 mg/g on a wet basis, respectively) followed by pericarp and aril. In mangosteen fruit with yellow gum inside, xanthones seemed to have shifted from the pericarp and to have concentrated in a gum on the surface of aril, and there was almost no difference between the amounts of alpha-mangostin and gamma-mangostin in whole fruits with and without yellow gum. Pericarp and yellow gum showed much higher radical-scavenging activity and ferric reducing antioxidant potential than the aril. (+info)
The effect of gartanin, a naturally occurring xanthone in mangosteen juice, on the mTOR pathway, autophagy, apoptosis, and the growth of human urinary bladder cancer cell lines.
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