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J Nat Prod. 2010 Mar 26;73(3):452-5. doi: 10.1021/np900404e.

Activity of mangosteen xanthones and teleocidin a-2 in death receptor expression enhancement and tumor necrosis factor related apoptosis-inducing ligand assays.

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  • 1Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.


A screening study using a luciferase assay to identify natural products that enhance death receptor 5 (DR5) expression was carried out, and bioassay-guided fractionation of two organisms, the pericarp of Garcinia mangostana (mangosteen) and actinomycete CKK609 strain, led to the isolation of eight xanthone derivatives (1-8) and teleocidin A-2 (9). Among them, compounds 1, 2, and 5, isolated from G. mangostana, and 9, from the actinomycete, showed potent DR5 promoter activity. Furthermore, we revealed that combined treatment with gartanin (5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) showed a potentiation effect in sensitizing TRAIL-resistant human gastric adenocarcinoma (AGS) cells. Thus, the present results suggested that 5 has the ability to overcome TRAIL resistance via the up-regulation of DR5 and may be an effective sensitizer of TRAIL-resistant cells.

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