Activity of Mangosteen Xanthones and Teleocidin A-2 in Death Receptor Expression Enhancement and Tumor Necrosis Factor Related Apoptosis-Inducing Ligand Assays

A screening study using luciferase assay to identify natural products dial enhance death receptor 5 (DR5) expression was carried out, and bioassay-induced fractionation of two organisms, the pericarp of Garcinia mangostana (mangosteen) and actinomycetc 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 front G. mangostana, and 9, from the actinomycete, showed potent DR5 promoter activity. Furthermore, we revealed that combined treatment with gartanin (5) and tumour 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.